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Study confirms prognostic impact of MYC partner gene in DLBCL
MYC rearrangement (MYC-R) has negative prognostic significance in patients with diffuse large B-cell lymphoma (DLBCL) in relation to the MYC partner gene, according to a retrospective study.
The negative prognostic effect of MYC-R was largely limited to patients with MYC–double hit/MYC–triple hit status and an immunoglobulin (IG) partner within 24 months following diagnosis.
“The primary objective of the study was to validate the prognostic relevance of [MYC–single hit] and [MYC–double hit/MYC–triple hit] status within the context of the MYC translocation partner (MYC-IG v. MYC-non-IG) in patients with DLBCL morphology,” wrote Andreas Rosenwald, MD, of the University of Würzburg (Germany) and colleagues in the Journal of Clinical Oncology.
The researchers identified 5,117 patients who all received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP–like immunochemotherapy, 2,383 of whom were evaluable for MYC-R and had complete clinical data. The cohort consisted of patients enrolled in various population-based registries and prospective clinical studies throughout North America and Europe.
The team used fluorescence in situ hybridization testing to identify MYC-R, in addition to BCL2 and/or BCL6 translocations if MYC-R was detected. Subsequently, these data were correlated with clinical endpoints.
After analysis, the researchers found that MYC-R was detected in 11% of patients. The presence of MYC-R was associated with significantly reduced survival, particularly within the initial 24 months following diagnosis.
Adverse prognostic implications were largely apparent in patients with accompanying rearrangement of BCL2 and/or BCL6 translocations (MYC–double-hit/MYC–triple hit status) and an immunoglobulin (IG) partner (hazard ratio, 2.4; 95% confidence interval, 1.6-3.6; P less than .001).
“These data suggest that little justification exists for altering initial therapeutic approaches in patients with DLBCL whose tumors carry an MYC translocation alone [MYC single hit],” they wrote. “However, for [MYC double hit/MYC triple hit] DLBCL, the major negative prognostic impact and 2-year effect support the practice of optimizing first-line treatment approaches to achieve maximum complete response rates because salvage treatment at relapse is not effective.”
Dr. Rosenwald and colleagues suggested that, in the future, diagnostic approaches should be implemented to detect patients in this high-risk group and that risk-modified treatment strategies should be further developed.
The study was supported by unrestricted grants to the Lunenburg Lymphoma Biomarker Consortium from several pharmaceutical companies and Bloodwise. Dr. Rosenwald reported having no conflicts of interest, but several coauthors reported relationships with industry.
SOURCE: : Rosenwald A et al. J Clin Oncol. 2019 Sep 9. doi: 10.1200/JCO.19.00743.
MYC rearrangement (MYC-R) has negative prognostic significance in patients with diffuse large B-cell lymphoma (DLBCL) in relation to the MYC partner gene, according to a retrospective study.
The negative prognostic effect of MYC-R was largely limited to patients with MYC–double hit/MYC–triple hit status and an immunoglobulin (IG) partner within 24 months following diagnosis.
“The primary objective of the study was to validate the prognostic relevance of [MYC–single hit] and [MYC–double hit/MYC–triple hit] status within the context of the MYC translocation partner (MYC-IG v. MYC-non-IG) in patients with DLBCL morphology,” wrote Andreas Rosenwald, MD, of the University of Würzburg (Germany) and colleagues in the Journal of Clinical Oncology.
The researchers identified 5,117 patients who all received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP–like immunochemotherapy, 2,383 of whom were evaluable for MYC-R and had complete clinical data. The cohort consisted of patients enrolled in various population-based registries and prospective clinical studies throughout North America and Europe.
The team used fluorescence in situ hybridization testing to identify MYC-R, in addition to BCL2 and/or BCL6 translocations if MYC-R was detected. Subsequently, these data were correlated with clinical endpoints.
After analysis, the researchers found that MYC-R was detected in 11% of patients. The presence of MYC-R was associated with significantly reduced survival, particularly within the initial 24 months following diagnosis.
Adverse prognostic implications were largely apparent in patients with accompanying rearrangement of BCL2 and/or BCL6 translocations (MYC–double-hit/MYC–triple hit status) and an immunoglobulin (IG) partner (hazard ratio, 2.4; 95% confidence interval, 1.6-3.6; P less than .001).
“These data suggest that little justification exists for altering initial therapeutic approaches in patients with DLBCL whose tumors carry an MYC translocation alone [MYC single hit],” they wrote. “However, for [MYC double hit/MYC triple hit] DLBCL, the major negative prognostic impact and 2-year effect support the practice of optimizing first-line treatment approaches to achieve maximum complete response rates because salvage treatment at relapse is not effective.”
Dr. Rosenwald and colleagues suggested that, in the future, diagnostic approaches should be implemented to detect patients in this high-risk group and that risk-modified treatment strategies should be further developed.
The study was supported by unrestricted grants to the Lunenburg Lymphoma Biomarker Consortium from several pharmaceutical companies and Bloodwise. Dr. Rosenwald reported having no conflicts of interest, but several coauthors reported relationships with industry.
SOURCE: : Rosenwald A et al. J Clin Oncol. 2019 Sep 9. doi: 10.1200/JCO.19.00743.
MYC rearrangement (MYC-R) has negative prognostic significance in patients with diffuse large B-cell lymphoma (DLBCL) in relation to the MYC partner gene, according to a retrospective study.
The negative prognostic effect of MYC-R was largely limited to patients with MYC–double hit/MYC–triple hit status and an immunoglobulin (IG) partner within 24 months following diagnosis.
“The primary objective of the study was to validate the prognostic relevance of [MYC–single hit] and [MYC–double hit/MYC–triple hit] status within the context of the MYC translocation partner (MYC-IG v. MYC-non-IG) in patients with DLBCL morphology,” wrote Andreas Rosenwald, MD, of the University of Würzburg (Germany) and colleagues in the Journal of Clinical Oncology.
The researchers identified 5,117 patients who all received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP–like immunochemotherapy, 2,383 of whom were evaluable for MYC-R and had complete clinical data. The cohort consisted of patients enrolled in various population-based registries and prospective clinical studies throughout North America and Europe.
The team used fluorescence in situ hybridization testing to identify MYC-R, in addition to BCL2 and/or BCL6 translocations if MYC-R was detected. Subsequently, these data were correlated with clinical endpoints.
After analysis, the researchers found that MYC-R was detected in 11% of patients. The presence of MYC-R was associated with significantly reduced survival, particularly within the initial 24 months following diagnosis.
Adverse prognostic implications were largely apparent in patients with accompanying rearrangement of BCL2 and/or BCL6 translocations (MYC–double-hit/MYC–triple hit status) and an immunoglobulin (IG) partner (hazard ratio, 2.4; 95% confidence interval, 1.6-3.6; P less than .001).
“These data suggest that little justification exists for altering initial therapeutic approaches in patients with DLBCL whose tumors carry an MYC translocation alone [MYC single hit],” they wrote. “However, for [MYC double hit/MYC triple hit] DLBCL, the major negative prognostic impact and 2-year effect support the practice of optimizing first-line treatment approaches to achieve maximum complete response rates because salvage treatment at relapse is not effective.”
Dr. Rosenwald and colleagues suggested that, in the future, diagnostic approaches should be implemented to detect patients in this high-risk group and that risk-modified treatment strategies should be further developed.
The study was supported by unrestricted grants to the Lunenburg Lymphoma Biomarker Consortium from several pharmaceutical companies and Bloodwise. Dr. Rosenwald reported having no conflicts of interest, but several coauthors reported relationships with industry.
SOURCE: : Rosenwald A et al. J Clin Oncol. 2019 Sep 9. doi: 10.1200/JCO.19.00743.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
VRD pretransplant induction deepens responses in myeloma
Pretransplant induction therapy with subcutaneous bortezomib, lenalidomide, and dexamethasone (VRD) deepened responses in patients with newly diagnosed multiple myeloma, according to an interim analysis of a phase 3 study.
Overall, the regimen was well tolerated, with a minimal number of patients discontinuing treatment because of treatment-emergent adverse events.
The ongoing, open-label, randomized, phase 3 study is designed to compare two transplant-conditioning regimens – intravenous busulfan plus melphalan versus melphalan – in patients who received VRD induction and consolidation, wrote Laura Rosiñol, MD, PhD, of the August Pi i Sunyer Biomedical Research Institute in Barcelona, and colleagues. The findings were published in Blood.
The PETHEMA/GEM2012 study included 458 patients with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplantation. Study patients were previously untreated and aged younger than 65 years.
All patients received VRD induction, which consisted of subcutaneous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of each cycle; lenalidomide 25 mg/day on days 1-21; and dexamethasone 40 mg on days 1-4 and 9-12 at 4-week intervals for six cycles. Posttransplant consolidation consisted of two cycles of VRD.
The researchers conducted a grouped-response analysis of three different treatment phases: induction, transplant, and consolidation.
After analysis, the researchers found that responses deepened over the duration of treatment. In patients who started the sixth induction cycle, the response rates were 55.6%, 63.8%, 68.3%, and 70.4% after cycles 3, 4, 5, and post induction, respectively.
After six cycles of induction, the complete response rate was 33.4%, with a rate of undetectable minimal residual disease of 28.8%, which further increased at transplant (42.1%), and consolidation (45.2%).
With respect to safety, the most frequently reported grade 3 or higher treatment-emergent adverse events were neutropenia (12.9%) and infection (9.2%). The rate of grade 2 or higher peripheral neuropathy throughout induction was 17.0%, with lower rates of grade 3 (3.7%) and 4 (0.2%) toxicities.
“The regimen [used in the present study] has the highest lenalidomide and dexamethasone dose intensity per cycle and a lower bortezomib dose intensity per cycle than the 21-day regimens, which may offer high activity with low levels of toxicity, thereby enabling delivery of all planned induction cycles,” the researchers wrote, adding that “these results confirm that VRD is an effective pretransplant induction regimen and may be considered a new standard of care.”
The study was supported by Celgene, Janssen, Pierre Fabré, and the Instituto de Salud Carlos III. The authors reported financial affiliations with Celgene, Janssen, and several other companies.
SOURCE: Rosiñol L et al. Blood. 2019 Sep 4. doi: 10.1182/blood.2019000241.
Pretransplant induction therapy with subcutaneous bortezomib, lenalidomide, and dexamethasone (VRD) deepened responses in patients with newly diagnosed multiple myeloma, according to an interim analysis of a phase 3 study.
Overall, the regimen was well tolerated, with a minimal number of patients discontinuing treatment because of treatment-emergent adverse events.
The ongoing, open-label, randomized, phase 3 study is designed to compare two transplant-conditioning regimens – intravenous busulfan plus melphalan versus melphalan – in patients who received VRD induction and consolidation, wrote Laura Rosiñol, MD, PhD, of the August Pi i Sunyer Biomedical Research Institute in Barcelona, and colleagues. The findings were published in Blood.
The PETHEMA/GEM2012 study included 458 patients with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplantation. Study patients were previously untreated and aged younger than 65 years.
All patients received VRD induction, which consisted of subcutaneous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of each cycle; lenalidomide 25 mg/day on days 1-21; and dexamethasone 40 mg on days 1-4 and 9-12 at 4-week intervals for six cycles. Posttransplant consolidation consisted of two cycles of VRD.
The researchers conducted a grouped-response analysis of three different treatment phases: induction, transplant, and consolidation.
After analysis, the researchers found that responses deepened over the duration of treatment. In patients who started the sixth induction cycle, the response rates were 55.6%, 63.8%, 68.3%, and 70.4% after cycles 3, 4, 5, and post induction, respectively.
After six cycles of induction, the complete response rate was 33.4%, with a rate of undetectable minimal residual disease of 28.8%, which further increased at transplant (42.1%), and consolidation (45.2%).
With respect to safety, the most frequently reported grade 3 or higher treatment-emergent adverse events were neutropenia (12.9%) and infection (9.2%). The rate of grade 2 or higher peripheral neuropathy throughout induction was 17.0%, with lower rates of grade 3 (3.7%) and 4 (0.2%) toxicities.
“The regimen [used in the present study] has the highest lenalidomide and dexamethasone dose intensity per cycle and a lower bortezomib dose intensity per cycle than the 21-day regimens, which may offer high activity with low levels of toxicity, thereby enabling delivery of all planned induction cycles,” the researchers wrote, adding that “these results confirm that VRD is an effective pretransplant induction regimen and may be considered a new standard of care.”
The study was supported by Celgene, Janssen, Pierre Fabré, and the Instituto de Salud Carlos III. The authors reported financial affiliations with Celgene, Janssen, and several other companies.
SOURCE: Rosiñol L et al. Blood. 2019 Sep 4. doi: 10.1182/blood.2019000241.
Pretransplant induction therapy with subcutaneous bortezomib, lenalidomide, and dexamethasone (VRD) deepened responses in patients with newly diagnosed multiple myeloma, according to an interim analysis of a phase 3 study.
Overall, the regimen was well tolerated, with a minimal number of patients discontinuing treatment because of treatment-emergent adverse events.
The ongoing, open-label, randomized, phase 3 study is designed to compare two transplant-conditioning regimens – intravenous busulfan plus melphalan versus melphalan – in patients who received VRD induction and consolidation, wrote Laura Rosiñol, MD, PhD, of the August Pi i Sunyer Biomedical Research Institute in Barcelona, and colleagues. The findings were published in Blood.
The PETHEMA/GEM2012 study included 458 patients with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplantation. Study patients were previously untreated and aged younger than 65 years.
All patients received VRD induction, which consisted of subcutaneous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of each cycle; lenalidomide 25 mg/day on days 1-21; and dexamethasone 40 mg on days 1-4 and 9-12 at 4-week intervals for six cycles. Posttransplant consolidation consisted of two cycles of VRD.
The researchers conducted a grouped-response analysis of three different treatment phases: induction, transplant, and consolidation.
After analysis, the researchers found that responses deepened over the duration of treatment. In patients who started the sixth induction cycle, the response rates were 55.6%, 63.8%, 68.3%, and 70.4% after cycles 3, 4, 5, and post induction, respectively.
After six cycles of induction, the complete response rate was 33.4%, with a rate of undetectable minimal residual disease of 28.8%, which further increased at transplant (42.1%), and consolidation (45.2%).
With respect to safety, the most frequently reported grade 3 or higher treatment-emergent adverse events were neutropenia (12.9%) and infection (9.2%). The rate of grade 2 or higher peripheral neuropathy throughout induction was 17.0%, with lower rates of grade 3 (3.7%) and 4 (0.2%) toxicities.
“The regimen [used in the present study] has the highest lenalidomide and dexamethasone dose intensity per cycle and a lower bortezomib dose intensity per cycle than the 21-day regimens, which may offer high activity with low levels of toxicity, thereby enabling delivery of all planned induction cycles,” the researchers wrote, adding that “these results confirm that VRD is an effective pretransplant induction regimen and may be considered a new standard of care.”
The study was supported by Celgene, Janssen, Pierre Fabré, and the Instituto de Salud Carlos III. The authors reported financial affiliations with Celgene, Janssen, and several other companies.
SOURCE: Rosiñol L et al. Blood. 2019 Sep 4. doi: 10.1182/blood.2019000241.
FROM BLOOD
Stem cells gene edited to be HIV resistant treat ALL, but not HIV
Gene editing of donor stem cells prior to transplantation into a patient with both HIV infection and acute lymphoblastic leukemia (ALL) was safe and effectively treated the patient’s leukemia, but failed to resolve his HIV, investigators reported.
The 27-year-old man received an HLA-matched transplant of hematopoietic stem and progenitor cells (HSPCs) that had been genetically engineered to lack CCR5, a key gateway for HIV entry into cells.
Although the transplant resulted in complete remission of leukemia with full donor chimerism, only about 9% of the posttransplant lymphocytes showed disruption of CCR5, and during a brief trial of antiretroviral therapy interruption his HIV viral load rebounded, reported Hongkui Deng, PhD, and colleagues from Peking University in China.
Although the experiment did not meet its goal of a drug-free HIV remission, it serves as a proof of concept for the use of CRISPR-Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9) gene editing to treat HIV infection, the authors contend.
“These results show the proof of principle that transplantation and long-term engraftment of CRISPR-edited allogeneic HSPCs can be achieved; however, the efficiency of the response was not adequate to achieve the target of cure of HIV-1 infection,” they wrote in a brief report published in the New England Journal of Medicine.
As previously reported, other research groups have investigated genetic editing to mimic a naturally occurring mutation that effectively disables the CCR5 HIV coreceptor, preventing the retrovirus from entering healthy cells. The mutation was first identified in a man named Timothy Brown who came to be known as “the Berlin patient” after he was apparently cured of HIV infection after a bone marrow transplant from a donor who had the mutation.
Dr. Deng and colleagues took advantage of HSPC transplantation, a standard therapy for ALL to see whether it could also have beneficial effects on concomitant HIV infection.
They treated donor HSPCs with CRISPR-Cas9 to ablate CCR5 and then delivered them to the patient along with additional CD34-depleted donor cells from mobilized peripheral blood.
The transplant was a success, with neutrophil engraftment on day 13 and platelet engraftment on day 27, and the leukemia was in morphologic complete remission at week 4 following transplantation. The patient remained in complete remission from leukemia throughout the 19-month follow-up period, with full donor chimerism .
However, when a planned interruption of antiretroviral therapy was carried out at 7 months post transplant, the serum viral load increased to 3 × 107 copies/ml at week 4 following interruption, and the patient was restarted on the drug. His viral levels gradually decreased to undetectable level during the subsequent months.
The investigators noted that 2 weeks after the drug interruption trial was started there was a small increase in the percentage of CCR5 insertion/deletions.
“The low efficiency of gene editing in the patient may be due to the competitive engraftment of the coinfused HSPCs in CD34-depleted cells and the persistence of donor T cells. To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPR-Cas9 system and improve the transplantation protocol,” they wrote.
The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.
SOURCE: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.
Gene editing of donor stem cells prior to transplantation into a patient with both HIV infection and acute lymphoblastic leukemia (ALL) was safe and effectively treated the patient’s leukemia, but failed to resolve his HIV, investigators reported.
The 27-year-old man received an HLA-matched transplant of hematopoietic stem and progenitor cells (HSPCs) that had been genetically engineered to lack CCR5, a key gateway for HIV entry into cells.
Although the transplant resulted in complete remission of leukemia with full donor chimerism, only about 9% of the posttransplant lymphocytes showed disruption of CCR5, and during a brief trial of antiretroviral therapy interruption his HIV viral load rebounded, reported Hongkui Deng, PhD, and colleagues from Peking University in China.
Although the experiment did not meet its goal of a drug-free HIV remission, it serves as a proof of concept for the use of CRISPR-Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9) gene editing to treat HIV infection, the authors contend.
“These results show the proof of principle that transplantation and long-term engraftment of CRISPR-edited allogeneic HSPCs can be achieved; however, the efficiency of the response was not adequate to achieve the target of cure of HIV-1 infection,” they wrote in a brief report published in the New England Journal of Medicine.
As previously reported, other research groups have investigated genetic editing to mimic a naturally occurring mutation that effectively disables the CCR5 HIV coreceptor, preventing the retrovirus from entering healthy cells. The mutation was first identified in a man named Timothy Brown who came to be known as “the Berlin patient” after he was apparently cured of HIV infection after a bone marrow transplant from a donor who had the mutation.
Dr. Deng and colleagues took advantage of HSPC transplantation, a standard therapy for ALL to see whether it could also have beneficial effects on concomitant HIV infection.
They treated donor HSPCs with CRISPR-Cas9 to ablate CCR5 and then delivered them to the patient along with additional CD34-depleted donor cells from mobilized peripheral blood.
The transplant was a success, with neutrophil engraftment on day 13 and platelet engraftment on day 27, and the leukemia was in morphologic complete remission at week 4 following transplantation. The patient remained in complete remission from leukemia throughout the 19-month follow-up period, with full donor chimerism .
However, when a planned interruption of antiretroviral therapy was carried out at 7 months post transplant, the serum viral load increased to 3 × 107 copies/ml at week 4 following interruption, and the patient was restarted on the drug. His viral levels gradually decreased to undetectable level during the subsequent months.
The investigators noted that 2 weeks after the drug interruption trial was started there was a small increase in the percentage of CCR5 insertion/deletions.
“The low efficiency of gene editing in the patient may be due to the competitive engraftment of the coinfused HSPCs in CD34-depleted cells and the persistence of donor T cells. To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPR-Cas9 system and improve the transplantation protocol,” they wrote.
The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.
SOURCE: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.
Gene editing of donor stem cells prior to transplantation into a patient with both HIV infection and acute lymphoblastic leukemia (ALL) was safe and effectively treated the patient’s leukemia, but failed to resolve his HIV, investigators reported.
The 27-year-old man received an HLA-matched transplant of hematopoietic stem and progenitor cells (HSPCs) that had been genetically engineered to lack CCR5, a key gateway for HIV entry into cells.
Although the transplant resulted in complete remission of leukemia with full donor chimerism, only about 9% of the posttransplant lymphocytes showed disruption of CCR5, and during a brief trial of antiretroviral therapy interruption his HIV viral load rebounded, reported Hongkui Deng, PhD, and colleagues from Peking University in China.
Although the experiment did not meet its goal of a drug-free HIV remission, it serves as a proof of concept for the use of CRISPR-Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9) gene editing to treat HIV infection, the authors contend.
“These results show the proof of principle that transplantation and long-term engraftment of CRISPR-edited allogeneic HSPCs can be achieved; however, the efficiency of the response was not adequate to achieve the target of cure of HIV-1 infection,” they wrote in a brief report published in the New England Journal of Medicine.
As previously reported, other research groups have investigated genetic editing to mimic a naturally occurring mutation that effectively disables the CCR5 HIV coreceptor, preventing the retrovirus from entering healthy cells. The mutation was first identified in a man named Timothy Brown who came to be known as “the Berlin patient” after he was apparently cured of HIV infection after a bone marrow transplant from a donor who had the mutation.
Dr. Deng and colleagues took advantage of HSPC transplantation, a standard therapy for ALL to see whether it could also have beneficial effects on concomitant HIV infection.
They treated donor HSPCs with CRISPR-Cas9 to ablate CCR5 and then delivered them to the patient along with additional CD34-depleted donor cells from mobilized peripheral blood.
The transplant was a success, with neutrophil engraftment on day 13 and platelet engraftment on day 27, and the leukemia was in morphologic complete remission at week 4 following transplantation. The patient remained in complete remission from leukemia throughout the 19-month follow-up period, with full donor chimerism .
However, when a planned interruption of antiretroviral therapy was carried out at 7 months post transplant, the serum viral load increased to 3 × 107 copies/ml at week 4 following interruption, and the patient was restarted on the drug. His viral levels gradually decreased to undetectable level during the subsequent months.
The investigators noted that 2 weeks after the drug interruption trial was started there was a small increase in the percentage of CCR5 insertion/deletions.
“The low efficiency of gene editing in the patient may be due to the competitive engraftment of the coinfused HSPCs in CD34-depleted cells and the persistence of donor T cells. To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPR-Cas9 system and improve the transplantation protocol,” they wrote.
The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.
SOURCE: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Donor cells depleted of the HIV coreceptor CCR5 effectively treated ALL, but not HIV.
Major finding: The patient had a sustained complete remission of ALL, but HIV persisted after transplantation.
Study details: Case report of a 27-year-old man with ALL and HIV.
Disclosures: The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.
Source: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.
Nonmyeloablative conditioning carries lowers infection risk in patients with AML
For patients with acute myeloid leukemia (AML) in need of allogeneic hematopoietic cell transplantation (alloHCT), reduced-intensity/nonmyeloablative conditioning (RIC/NMA) offers a lower risk of infection than myeloablative conditioning (MAC), based on a retrospective study involving more than 1,700 patients.
Within 100 days of treatment, patients who underwent MAC were significantly more likely to develop a bacterial infection, and develop it at an earlier date, than patients who had undergone RIC/NMA, reported lead author Celalettin Ustun, MD, of Rush University in Chicago, and colleagues.
“The incidence of infections, a common and often severe complication of alloHCT, is expected to be lower after RIC/NMA compared with MAC and thus contribute to the decreased [nonrelapse mortality],” the investigators wrote in Blood Advances, noting that this hypothesis has previously lacked supporting data, prompting the present study.
The retrospective analysis involved 1,755 patients with AML who were in first complete remission. Data were drawn from the Center for International Blood and Marrow Transplant Research (CIBMTR). The primary end point was incidence of infection within 100 days after T-cell replete alloHCT in patients receiving MAC (n = 978) versus those who underwent RIC/NMA (n = 777). Secondary end points included comparisons of infection types and infection density.
Patients who received RIC/NMA were generally older and more likely to have myelodysplastic syndrome than patients in the MAC group; the groups were otherwise similar, based on comorbidities, cytogenetic risks, and Karnofsky performance scores.
The proportion of patients who developed at least one infection was comparable between groups: 61% of MAC patients versus 58% of RIC/NMA patients (P = .21), but further analysis showed that MAC was in fact associated with some relatively increased risks. For instance, patients in the MAC group tended to develop infections sooner than patients treated with RIC/NMA (21 vs. 15 days), and more patients treated with MAC had at least one bacterial infection by day 100 (46% vs. 37%).
Although the proportion of patients developing at least one viral infection was slightly lower in the MAC group than the RIC/NMA group (34% vs. 39%), overall infection density was higher, which takes into account multiple infections.
The increased bacterial infections after MAC were caused by gram-positive bacteria, while the increased viral infections with RIC/NMA were caused by cytomegalovirus, the investigators reported.
“RIC/NMA alloHCT is associated with a decreased risk of any infection and particularly early bacterial infections,” the investigators wrote. “The risk of viral and fungal infections per days at risk is similar.”
The Center for International Blood and Marrow Transplant Research is supported by grants from the U.S. government and several pharmaceutical companies. The investigators reported having no conflicts of interest.
SOURCE: Ustun C et al. Blood Adv. 2019 Sep 10;3(17):2525-36.
For patients with acute myeloid leukemia (AML) in need of allogeneic hematopoietic cell transplantation (alloHCT), reduced-intensity/nonmyeloablative conditioning (RIC/NMA) offers a lower risk of infection than myeloablative conditioning (MAC), based on a retrospective study involving more than 1,700 patients.
Within 100 days of treatment, patients who underwent MAC were significantly more likely to develop a bacterial infection, and develop it at an earlier date, than patients who had undergone RIC/NMA, reported lead author Celalettin Ustun, MD, of Rush University in Chicago, and colleagues.
“The incidence of infections, a common and often severe complication of alloHCT, is expected to be lower after RIC/NMA compared with MAC and thus contribute to the decreased [nonrelapse mortality],” the investigators wrote in Blood Advances, noting that this hypothesis has previously lacked supporting data, prompting the present study.
The retrospective analysis involved 1,755 patients with AML who were in first complete remission. Data were drawn from the Center for International Blood and Marrow Transplant Research (CIBMTR). The primary end point was incidence of infection within 100 days after T-cell replete alloHCT in patients receiving MAC (n = 978) versus those who underwent RIC/NMA (n = 777). Secondary end points included comparisons of infection types and infection density.
Patients who received RIC/NMA were generally older and more likely to have myelodysplastic syndrome than patients in the MAC group; the groups were otherwise similar, based on comorbidities, cytogenetic risks, and Karnofsky performance scores.
The proportion of patients who developed at least one infection was comparable between groups: 61% of MAC patients versus 58% of RIC/NMA patients (P = .21), but further analysis showed that MAC was in fact associated with some relatively increased risks. For instance, patients in the MAC group tended to develop infections sooner than patients treated with RIC/NMA (21 vs. 15 days), and more patients treated with MAC had at least one bacterial infection by day 100 (46% vs. 37%).
Although the proportion of patients developing at least one viral infection was slightly lower in the MAC group than the RIC/NMA group (34% vs. 39%), overall infection density was higher, which takes into account multiple infections.
The increased bacterial infections after MAC were caused by gram-positive bacteria, while the increased viral infections with RIC/NMA were caused by cytomegalovirus, the investigators reported.
“RIC/NMA alloHCT is associated with a decreased risk of any infection and particularly early bacterial infections,” the investigators wrote. “The risk of viral and fungal infections per days at risk is similar.”
The Center for International Blood and Marrow Transplant Research is supported by grants from the U.S. government and several pharmaceutical companies. The investigators reported having no conflicts of interest.
SOURCE: Ustun C et al. Blood Adv. 2019 Sep 10;3(17):2525-36.
For patients with acute myeloid leukemia (AML) in need of allogeneic hematopoietic cell transplantation (alloHCT), reduced-intensity/nonmyeloablative conditioning (RIC/NMA) offers a lower risk of infection than myeloablative conditioning (MAC), based on a retrospective study involving more than 1,700 patients.
Within 100 days of treatment, patients who underwent MAC were significantly more likely to develop a bacterial infection, and develop it at an earlier date, than patients who had undergone RIC/NMA, reported lead author Celalettin Ustun, MD, of Rush University in Chicago, and colleagues.
“The incidence of infections, a common and often severe complication of alloHCT, is expected to be lower after RIC/NMA compared with MAC and thus contribute to the decreased [nonrelapse mortality],” the investigators wrote in Blood Advances, noting that this hypothesis has previously lacked supporting data, prompting the present study.
The retrospective analysis involved 1,755 patients with AML who were in first complete remission. Data were drawn from the Center for International Blood and Marrow Transplant Research (CIBMTR). The primary end point was incidence of infection within 100 days after T-cell replete alloHCT in patients receiving MAC (n = 978) versus those who underwent RIC/NMA (n = 777). Secondary end points included comparisons of infection types and infection density.
Patients who received RIC/NMA were generally older and more likely to have myelodysplastic syndrome than patients in the MAC group; the groups were otherwise similar, based on comorbidities, cytogenetic risks, and Karnofsky performance scores.
The proportion of patients who developed at least one infection was comparable between groups: 61% of MAC patients versus 58% of RIC/NMA patients (P = .21), but further analysis showed that MAC was in fact associated with some relatively increased risks. For instance, patients in the MAC group tended to develop infections sooner than patients treated with RIC/NMA (21 vs. 15 days), and more patients treated with MAC had at least one bacterial infection by day 100 (46% vs. 37%).
Although the proportion of patients developing at least one viral infection was slightly lower in the MAC group than the RIC/NMA group (34% vs. 39%), overall infection density was higher, which takes into account multiple infections.
The increased bacterial infections after MAC were caused by gram-positive bacteria, while the increased viral infections with RIC/NMA were caused by cytomegalovirus, the investigators reported.
“RIC/NMA alloHCT is associated with a decreased risk of any infection and particularly early bacterial infections,” the investigators wrote. “The risk of viral and fungal infections per days at risk is similar.”
The Center for International Blood and Marrow Transplant Research is supported by grants from the U.S. government and several pharmaceutical companies. The investigators reported having no conflicts of interest.
SOURCE: Ustun C et al. Blood Adv. 2019 Sep 10;3(17):2525-36.
FROM BLOOD ADVANCES
Key clinical point: For patients with acute myeloid leukemia (AML) in need of allogeneic hematopoietic cell transplantation (alloHCT), reduced-intensity/nonmyeloablative conditioning (RIC/NMA) offers a lower risk of infection than myeloablative conditioning (MAC).
Major finding: By day 100, 37% of patients who received RIC/NMA had at least one bacterial infection, compared with 46% of patients who underwent MAC (P = .0004).
Study details: A retrospective study involving 1,755 patients with AML in first complete remission.
Disclosures: The Center for International Blood and Marrow Transplant Research is supported by grants from the U.S. government and several pharmaceutical companies. The investigators reported having no conflicts of interest.
Source: Ustun C et al. Blood Adv. 2019 Sep 3(17):2525-36.
U.S. and African programs aim to improve understanding, treatment of sickle cell disease
Researchers are leading several programs designed to serve the sickle cell community in the United States and sub-Saharan Africa, officials at the National Heart, Lung, and Blood Institute (NHLBI) said during a recent webinar.
One program based in the United States is focused on building a registry for patients with sickle cell disease (SCD) and conducting studies designed to improve SCD care. Another program involves building “an information-sharing network and patient-powered registry” in the United States.
The programs in sub-Saharan Africa were designed to establish a database of SCD patients, optimize the use of hydroxyurea in children with SCD, and aid genomic studies of SCD.
W. Keith Hoots, MD, director of the Division of Blood Diseases and Resources at NHLBI, began the webinar with an overview of the programs in sub-Saharan Africa. He described four programs with sites in nine countries (Angola, Cameroon, Democratic Republic of Congo, Ghana, Kenya, Nigeria, South Africa, Tanzania, and Uganda).
SPARCO and SADaCC
Dr. Hoots outlined the scope the Sickle Pan-African Research Consortium (SPARCO) and the Sickle Africa Data Coordinating Center (SADaCC), both part of the Sickle In Africa consortium.
A major goal of SPARCO and SADaCC is to create a Research Electronic Data Capture database that encompasses SCD patients in sub-Saharan Africa. As of April 2019, the database included 6,578 patients. The target is 13,000 patients.
Other goals of SPARCO and SADaCC are to “harmonize” SCD phenotype definitions and ontologies, create clinical guidelines for SCD management in sub-Saharan Africa, plan future cohort studies, and develop programs for newborn screening, infection prevention, and increased use of hydroxyurea.
“So far, they’re well along in establishing a registry and a database system,” Dr. Hoots said. “They’ve agreed on the database elements, phenotype definitions, and ontologies, they’ve developed some regionally appropriate clinical management guidelines, and they’ve begun skills development on the ground at all respective sites.”
REACH
Another program Dr. Hoots discussed is Realizing Effectiveness Across Continents With Hydroxyurea (REACH), a phase 1/2 pilot study of hydroxyurea in children (aged 1-10 years) with SCD in sub-Saharan Africa.
The goals of REACH are to determine the optimal dose of hydroxyurea in this population; teach African physicians how to administer hydroxyurea; assess the safety, feasibility, and benefits of hydroxyurea; study variability in response to hydroxyurea; gather data for the Research Electronic Data Capture database; and establish a research infrastructure for future collaborations.
Results from more than 600 children enrolled in REACH were presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2019 Jan 10; 380[2]:121-31).
SickleGenAfrica
SickleGenAfrica is part of the H3Africa consortium and aims to “build capacity for genomic research in Africa,” Dr. Hoots said.
Under this program, researchers will conduct three studies to test the hypothesis that genetic variation affects the defense against hemolysis and organ damage in patients with SCD. The researchers will study existing cohorts of SCD patients including children and adults.
Other goals of SickleGenAfrica are to establish a molecular hematology and sickle cell mouse core, an SCD biorepository core, a bioinformatics core, and an administrative core for the coordination of activities. The program will also be used to train “future science leaders” in SCD research, Dr. Hoots said.
SCDIC
Cheryl Anne Boyce, PhD, chief of the Implementation Science Branch at the Center for Translation Research and Implementation Science at NHLBI, discussed the United States–based Sickle Cell Disease Implementation Consortium (SCDIC).
“The goals of the consortium are to develop a registry in collaboration with other centers and the NHLBI, as well as a needs-based community assessment of the barriers to care for subjects with sickle cell disease,” Dr. Boyce said. “We also wanted to design implementation research studies that address the identified barriers to care.”
Dr. Boyce said the SCDIC’s registry is open to patients aged 15-45 years who have a confirmed SCD diagnosis, speak English, and are able to consent to and complete a survey. The registry has enrolled almost 2,400 patients from eight centers over 18 months.
The SCDIC has also performed a needs assessment that prompted the development of three implementation research studies. The first study involves using mobile health interventions to, ideally, increase patient adherence to hydroxyurea and improve provider knowledge of hydroxyurea.
With the second study, researchers aim to improve the care of SCD patients in the emergency department by using an inpatient portal. The goals of the third study are to establish a standard definition for unaffiliated patients, conduct a needs assessment for this group, and develop an intervention that can provide these patients with guideline-based SCD care.
Get Connected
Kim Smith-Whitley, MD, director of the Comprehensive Sickle Cell Center at the Children’s Hospital of Philadelphia and a board member of the Sickle Cell Disease Association of America (SCDAA), described Get Connected, “an information-sharing network and patient-powered registry” created by SCDAA.
Dr. Smith-Whitley said one purpose of Get Connected is to provide a network that facilitates “the distribution of information related to clinical care, research, health services, health policy, and advocacy.”
The network is open to families living with SCD and sickle cell trait, SCDAA member organizations, health care providers, clinical researchers, and community-based organizations.
Get Connected also includes a registry for SCD patients that stores information on their diagnosis and treatment, as well as online communities that can be used to share information and provide psychosocial support.
Thus far, Get Connected has enrolled 6,329 individuals. This includes 5,100 children and adults with SCD, 652 children and adults with sickle cell trait, and 577 nonpatients.
The webinar presenters did not disclose any conflicts of interest.
Researchers are leading several programs designed to serve the sickle cell community in the United States and sub-Saharan Africa, officials at the National Heart, Lung, and Blood Institute (NHLBI) said during a recent webinar.
One program based in the United States is focused on building a registry for patients with sickle cell disease (SCD) and conducting studies designed to improve SCD care. Another program involves building “an information-sharing network and patient-powered registry” in the United States.
The programs in sub-Saharan Africa were designed to establish a database of SCD patients, optimize the use of hydroxyurea in children with SCD, and aid genomic studies of SCD.
W. Keith Hoots, MD, director of the Division of Blood Diseases and Resources at NHLBI, began the webinar with an overview of the programs in sub-Saharan Africa. He described four programs with sites in nine countries (Angola, Cameroon, Democratic Republic of Congo, Ghana, Kenya, Nigeria, South Africa, Tanzania, and Uganda).
SPARCO and SADaCC
Dr. Hoots outlined the scope the Sickle Pan-African Research Consortium (SPARCO) and the Sickle Africa Data Coordinating Center (SADaCC), both part of the Sickle In Africa consortium.
A major goal of SPARCO and SADaCC is to create a Research Electronic Data Capture database that encompasses SCD patients in sub-Saharan Africa. As of April 2019, the database included 6,578 patients. The target is 13,000 patients.
Other goals of SPARCO and SADaCC are to “harmonize” SCD phenotype definitions and ontologies, create clinical guidelines for SCD management in sub-Saharan Africa, plan future cohort studies, and develop programs for newborn screening, infection prevention, and increased use of hydroxyurea.
“So far, they’re well along in establishing a registry and a database system,” Dr. Hoots said. “They’ve agreed on the database elements, phenotype definitions, and ontologies, they’ve developed some regionally appropriate clinical management guidelines, and they’ve begun skills development on the ground at all respective sites.”
REACH
Another program Dr. Hoots discussed is Realizing Effectiveness Across Continents With Hydroxyurea (REACH), a phase 1/2 pilot study of hydroxyurea in children (aged 1-10 years) with SCD in sub-Saharan Africa.
The goals of REACH are to determine the optimal dose of hydroxyurea in this population; teach African physicians how to administer hydroxyurea; assess the safety, feasibility, and benefits of hydroxyurea; study variability in response to hydroxyurea; gather data for the Research Electronic Data Capture database; and establish a research infrastructure for future collaborations.
Results from more than 600 children enrolled in REACH were presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2019 Jan 10; 380[2]:121-31).
SickleGenAfrica
SickleGenAfrica is part of the H3Africa consortium and aims to “build capacity for genomic research in Africa,” Dr. Hoots said.
Under this program, researchers will conduct three studies to test the hypothesis that genetic variation affects the defense against hemolysis and organ damage in patients with SCD. The researchers will study existing cohorts of SCD patients including children and adults.
Other goals of SickleGenAfrica are to establish a molecular hematology and sickle cell mouse core, an SCD biorepository core, a bioinformatics core, and an administrative core for the coordination of activities. The program will also be used to train “future science leaders” in SCD research, Dr. Hoots said.
SCDIC
Cheryl Anne Boyce, PhD, chief of the Implementation Science Branch at the Center for Translation Research and Implementation Science at NHLBI, discussed the United States–based Sickle Cell Disease Implementation Consortium (SCDIC).
“The goals of the consortium are to develop a registry in collaboration with other centers and the NHLBI, as well as a needs-based community assessment of the barriers to care for subjects with sickle cell disease,” Dr. Boyce said. “We also wanted to design implementation research studies that address the identified barriers to care.”
Dr. Boyce said the SCDIC’s registry is open to patients aged 15-45 years who have a confirmed SCD diagnosis, speak English, and are able to consent to and complete a survey. The registry has enrolled almost 2,400 patients from eight centers over 18 months.
The SCDIC has also performed a needs assessment that prompted the development of three implementation research studies. The first study involves using mobile health interventions to, ideally, increase patient adherence to hydroxyurea and improve provider knowledge of hydroxyurea.
With the second study, researchers aim to improve the care of SCD patients in the emergency department by using an inpatient portal. The goals of the third study are to establish a standard definition for unaffiliated patients, conduct a needs assessment for this group, and develop an intervention that can provide these patients with guideline-based SCD care.
Get Connected
Kim Smith-Whitley, MD, director of the Comprehensive Sickle Cell Center at the Children’s Hospital of Philadelphia and a board member of the Sickle Cell Disease Association of America (SCDAA), described Get Connected, “an information-sharing network and patient-powered registry” created by SCDAA.
Dr. Smith-Whitley said one purpose of Get Connected is to provide a network that facilitates “the distribution of information related to clinical care, research, health services, health policy, and advocacy.”
The network is open to families living with SCD and sickle cell trait, SCDAA member organizations, health care providers, clinical researchers, and community-based organizations.
Get Connected also includes a registry for SCD patients that stores information on their diagnosis and treatment, as well as online communities that can be used to share information and provide psychosocial support.
Thus far, Get Connected has enrolled 6,329 individuals. This includes 5,100 children and adults with SCD, 652 children and adults with sickle cell trait, and 577 nonpatients.
The webinar presenters did not disclose any conflicts of interest.
Researchers are leading several programs designed to serve the sickle cell community in the United States and sub-Saharan Africa, officials at the National Heart, Lung, and Blood Institute (NHLBI) said during a recent webinar.
One program based in the United States is focused on building a registry for patients with sickle cell disease (SCD) and conducting studies designed to improve SCD care. Another program involves building “an information-sharing network and patient-powered registry” in the United States.
The programs in sub-Saharan Africa were designed to establish a database of SCD patients, optimize the use of hydroxyurea in children with SCD, and aid genomic studies of SCD.
W. Keith Hoots, MD, director of the Division of Blood Diseases and Resources at NHLBI, began the webinar with an overview of the programs in sub-Saharan Africa. He described four programs with sites in nine countries (Angola, Cameroon, Democratic Republic of Congo, Ghana, Kenya, Nigeria, South Africa, Tanzania, and Uganda).
SPARCO and SADaCC
Dr. Hoots outlined the scope the Sickle Pan-African Research Consortium (SPARCO) and the Sickle Africa Data Coordinating Center (SADaCC), both part of the Sickle In Africa consortium.
A major goal of SPARCO and SADaCC is to create a Research Electronic Data Capture database that encompasses SCD patients in sub-Saharan Africa. As of April 2019, the database included 6,578 patients. The target is 13,000 patients.
Other goals of SPARCO and SADaCC are to “harmonize” SCD phenotype definitions and ontologies, create clinical guidelines for SCD management in sub-Saharan Africa, plan future cohort studies, and develop programs for newborn screening, infection prevention, and increased use of hydroxyurea.
“So far, they’re well along in establishing a registry and a database system,” Dr. Hoots said. “They’ve agreed on the database elements, phenotype definitions, and ontologies, they’ve developed some regionally appropriate clinical management guidelines, and they’ve begun skills development on the ground at all respective sites.”
REACH
Another program Dr. Hoots discussed is Realizing Effectiveness Across Continents With Hydroxyurea (REACH), a phase 1/2 pilot study of hydroxyurea in children (aged 1-10 years) with SCD in sub-Saharan Africa.
The goals of REACH are to determine the optimal dose of hydroxyurea in this population; teach African physicians how to administer hydroxyurea; assess the safety, feasibility, and benefits of hydroxyurea; study variability in response to hydroxyurea; gather data for the Research Electronic Data Capture database; and establish a research infrastructure for future collaborations.
Results from more than 600 children enrolled in REACH were presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2019 Jan 10; 380[2]:121-31).
SickleGenAfrica
SickleGenAfrica is part of the H3Africa consortium and aims to “build capacity for genomic research in Africa,” Dr. Hoots said.
Under this program, researchers will conduct three studies to test the hypothesis that genetic variation affects the defense against hemolysis and organ damage in patients with SCD. The researchers will study existing cohorts of SCD patients including children and adults.
Other goals of SickleGenAfrica are to establish a molecular hematology and sickle cell mouse core, an SCD biorepository core, a bioinformatics core, and an administrative core for the coordination of activities. The program will also be used to train “future science leaders” in SCD research, Dr. Hoots said.
SCDIC
Cheryl Anne Boyce, PhD, chief of the Implementation Science Branch at the Center for Translation Research and Implementation Science at NHLBI, discussed the United States–based Sickle Cell Disease Implementation Consortium (SCDIC).
“The goals of the consortium are to develop a registry in collaboration with other centers and the NHLBI, as well as a needs-based community assessment of the barriers to care for subjects with sickle cell disease,” Dr. Boyce said. “We also wanted to design implementation research studies that address the identified barriers to care.”
Dr. Boyce said the SCDIC’s registry is open to patients aged 15-45 years who have a confirmed SCD diagnosis, speak English, and are able to consent to and complete a survey. The registry has enrolled almost 2,400 patients from eight centers over 18 months.
The SCDIC has also performed a needs assessment that prompted the development of three implementation research studies. The first study involves using mobile health interventions to, ideally, increase patient adherence to hydroxyurea and improve provider knowledge of hydroxyurea.
With the second study, researchers aim to improve the care of SCD patients in the emergency department by using an inpatient portal. The goals of the third study are to establish a standard definition for unaffiliated patients, conduct a needs assessment for this group, and develop an intervention that can provide these patients with guideline-based SCD care.
Get Connected
Kim Smith-Whitley, MD, director of the Comprehensive Sickle Cell Center at the Children’s Hospital of Philadelphia and a board member of the Sickle Cell Disease Association of America (SCDAA), described Get Connected, “an information-sharing network and patient-powered registry” created by SCDAA.
Dr. Smith-Whitley said one purpose of Get Connected is to provide a network that facilitates “the distribution of information related to clinical care, research, health services, health policy, and advocacy.”
The network is open to families living with SCD and sickle cell trait, SCDAA member organizations, health care providers, clinical researchers, and community-based organizations.
Get Connected also includes a registry for SCD patients that stores information on their diagnosis and treatment, as well as online communities that can be used to share information and provide psychosocial support.
Thus far, Get Connected has enrolled 6,329 individuals. This includes 5,100 children and adults with SCD, 652 children and adults with sickle cell trait, and 577 nonpatients.
The webinar presenters did not disclose any conflicts of interest.
Pediatric HSCT recipients still risking sunburn
Young people who have received allogeneic hematopoietic stem cell transplants (HSCTs) are more likely to wear hats, sunscreen and other sun protection, but still intentionally tan and experience sunburn at the same rate as their peers, new research suggests.
In a survey‐based, cross‐sectional cohort study, researchers compared sun-protection behaviors and sun exposure in 85 children aged 21 years and younger who had undergone HSCT and 85 age-, sex-, and skin type–matched controls. The findings were published in Pediatric Dermatology.
HSCT recipients have a higher risk of long-term complications such as skin cancer, for which sun exposure is a major modifiable environmental risk factor.
“Therefore, consistent sun avoidance and protection as well as regular dermatologic evaluations are important for HSCT recipients,” wrote Edward B. Li, PhD, from Harvard Medical School, Boston, and coauthors.
The survey found no significant difference between the transplant and control group in the amount of intentional sun exposure, such as the amount of time spent outside on weekdays and weekends during the peak sun intensity hours of 10 a.m. and 4 p.m. More than one in five transplant recipients (21.2%) reported spending at least 3 hours a day outside between 10 a.m. and 4 p.m. on weekdays, as did 36.5% of transplant recipients on weekends.
There were also no significant differences between the two groups in terms of time spent tanning, either in the sun or in a tanning bed. Additionally, a similar number of transplant recipients and controls experienced one or more red or painful sunburns in the past year (25.9% vs. 27.1%).
However, transplant patients did practice better sun protection behaviors than did the control group, with 60% reporting that they always wore sunscreen, compared with 29.4% of controls. The transplant recipients were also significantly more likely to wear sunglasses and a hat and to stay in the shade or use an umbrella.
“While these data may reflect that HSCT patients are not practicing adequate sun avoidance, it may also suggest that these long‐term survivors are able to enjoy being outdoors as much as their peers and have a similar desire to have a tanned appearance,” the researchers wrote. “While a healthy and active lifestyle should be encouraged for all children, our results emphasize the need for pediatric HSCT survivors to be educated on their increased risk for UV‐related skin cancers, counseled on avoidance of intentional tanning, and advised on the importance of sun protection behaviors in an effort to improve long-term outcomes.”
The researchers noted that transplant recipients were significantly more likely to have had a full body skin exam from a health care professional than were individuals in the control group (61.2% vs. 4.7%) and were more likely to have done a self-check or been checked by a partner in the previous year.
The study was supported by the Society for Pediatric Dermatology, the Dermatology Foundation, the National Institutes of Health, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. One author declared a financial interest in a company developing a dermatological product. No other conflicts of interest were declared.
SOURCE: Li EB et al. Pediatr Dermatol. 2019 Aug 13. doi: 10.1111/pde.13984.
Young people who have received allogeneic hematopoietic stem cell transplants (HSCTs) are more likely to wear hats, sunscreen and other sun protection, but still intentionally tan and experience sunburn at the same rate as their peers, new research suggests.
In a survey‐based, cross‐sectional cohort study, researchers compared sun-protection behaviors and sun exposure in 85 children aged 21 years and younger who had undergone HSCT and 85 age-, sex-, and skin type–matched controls. The findings were published in Pediatric Dermatology.
HSCT recipients have a higher risk of long-term complications such as skin cancer, for which sun exposure is a major modifiable environmental risk factor.
“Therefore, consistent sun avoidance and protection as well as regular dermatologic evaluations are important for HSCT recipients,” wrote Edward B. Li, PhD, from Harvard Medical School, Boston, and coauthors.
The survey found no significant difference between the transplant and control group in the amount of intentional sun exposure, such as the amount of time spent outside on weekdays and weekends during the peak sun intensity hours of 10 a.m. and 4 p.m. More than one in five transplant recipients (21.2%) reported spending at least 3 hours a day outside between 10 a.m. and 4 p.m. on weekdays, as did 36.5% of transplant recipients on weekends.
There were also no significant differences between the two groups in terms of time spent tanning, either in the sun or in a tanning bed. Additionally, a similar number of transplant recipients and controls experienced one or more red or painful sunburns in the past year (25.9% vs. 27.1%).
However, transplant patients did practice better sun protection behaviors than did the control group, with 60% reporting that they always wore sunscreen, compared with 29.4% of controls. The transplant recipients were also significantly more likely to wear sunglasses and a hat and to stay in the shade or use an umbrella.
“While these data may reflect that HSCT patients are not practicing adequate sun avoidance, it may also suggest that these long‐term survivors are able to enjoy being outdoors as much as their peers and have a similar desire to have a tanned appearance,” the researchers wrote. “While a healthy and active lifestyle should be encouraged for all children, our results emphasize the need for pediatric HSCT survivors to be educated on their increased risk for UV‐related skin cancers, counseled on avoidance of intentional tanning, and advised on the importance of sun protection behaviors in an effort to improve long-term outcomes.”
The researchers noted that transplant recipients were significantly more likely to have had a full body skin exam from a health care professional than were individuals in the control group (61.2% vs. 4.7%) and were more likely to have done a self-check or been checked by a partner in the previous year.
The study was supported by the Society for Pediatric Dermatology, the Dermatology Foundation, the National Institutes of Health, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. One author declared a financial interest in a company developing a dermatological product. No other conflicts of interest were declared.
SOURCE: Li EB et al. Pediatr Dermatol. 2019 Aug 13. doi: 10.1111/pde.13984.
Young people who have received allogeneic hematopoietic stem cell transplants (HSCTs) are more likely to wear hats, sunscreen and other sun protection, but still intentionally tan and experience sunburn at the same rate as their peers, new research suggests.
In a survey‐based, cross‐sectional cohort study, researchers compared sun-protection behaviors and sun exposure in 85 children aged 21 years and younger who had undergone HSCT and 85 age-, sex-, and skin type–matched controls. The findings were published in Pediatric Dermatology.
HSCT recipients have a higher risk of long-term complications such as skin cancer, for which sun exposure is a major modifiable environmental risk factor.
“Therefore, consistent sun avoidance and protection as well as regular dermatologic evaluations are important for HSCT recipients,” wrote Edward B. Li, PhD, from Harvard Medical School, Boston, and coauthors.
The survey found no significant difference between the transplant and control group in the amount of intentional sun exposure, such as the amount of time spent outside on weekdays and weekends during the peak sun intensity hours of 10 a.m. and 4 p.m. More than one in five transplant recipients (21.2%) reported spending at least 3 hours a day outside between 10 a.m. and 4 p.m. on weekdays, as did 36.5% of transplant recipients on weekends.
There were also no significant differences between the two groups in terms of time spent tanning, either in the sun or in a tanning bed. Additionally, a similar number of transplant recipients and controls experienced one or more red or painful sunburns in the past year (25.9% vs. 27.1%).
However, transplant patients did practice better sun protection behaviors than did the control group, with 60% reporting that they always wore sunscreen, compared with 29.4% of controls. The transplant recipients were also significantly more likely to wear sunglasses and a hat and to stay in the shade or use an umbrella.
“While these data may reflect that HSCT patients are not practicing adequate sun avoidance, it may also suggest that these long‐term survivors are able to enjoy being outdoors as much as their peers and have a similar desire to have a tanned appearance,” the researchers wrote. “While a healthy and active lifestyle should be encouraged for all children, our results emphasize the need for pediatric HSCT survivors to be educated on their increased risk for UV‐related skin cancers, counseled on avoidance of intentional tanning, and advised on the importance of sun protection behaviors in an effort to improve long-term outcomes.”
The researchers noted that transplant recipients were significantly more likely to have had a full body skin exam from a health care professional than were individuals in the control group (61.2% vs. 4.7%) and were more likely to have done a self-check or been checked by a partner in the previous year.
The study was supported by the Society for Pediatric Dermatology, the Dermatology Foundation, the National Institutes of Health, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. One author declared a financial interest in a company developing a dermatological product. No other conflicts of interest were declared.
SOURCE: Li EB et al. Pediatr Dermatol. 2019 Aug 13. doi: 10.1111/pde.13984.
FROM PEDIATRIC DERMATOLOGY
Rituximab, bendamustine look better than chemo alone in MCL
In older patients with newly diagnosed mantle cell lymphoma (MCL), first-line therapy with rituximab- and bendamustine-based regimens significantly reduced 1-year mortality rates versus chemotherapy alone, according to a retrospective analysis.
“This study evaluated the comparative effectiveness of [rituximab, bortezomib, or bendamustine] in elderly patients newly diagnosed with MCL,” wrote Shuangshuang Fu, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in Clinical Lymphoma, Myeloma & Leukemia.
The researchers studied population-based data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. They identified all patients over age 65 years who received a new diagnosis of MCL between Jan. 1, 1999, and Dec. 31, 2013.
The study cohort included a total of 1,215 patients. Participants were classified into four different groups according to treatment regimen: chemotherapy alone, rituximab plus or minus chemotherapy, bendamustine plus or minus chemotherapy, and bortezomib plus or minus chemotherapy.
At 1-year follow-up, the team analyzed various mortality outcomes, including MCL-specific, all-cause, and noncancer mortality. The bortezomib results were not included in the primary analysis because of small sample size, according to the researchers.
After multivariable analysis, Dr. Fu and colleagues found that 1-year all-cause mortality rate was significantly lower for patients receiving rituximab-based regimens, compared with chemotherapy alone (hazard ratio, 0.38; 95% confidence interval, 0.25-0.59). There was a similar decline for MCL-specific mortality (HR, 0.38; 95% CI, 0.24-0.60).
The 1-year MCL-specific mortality was also significantly reduced in the bendamustine group, compared with chemotherapy alone (HR, 0.49; 95% CI, 0.24-0.99).
“Our findings comparing rituximab with chemotherapy alone further confirmed the benefit of adding rituximab to chemotherapy in newly diagnosed older MCL patients,” they wrote.
The researchers acknowledged that a key limitation of the study was the observational design. As a result, selection bias and unmeasured confounding could have influenced the results.
“Future studies evaluating the comparative effectiveness of those newly approved novel agents for MCL patients were warranted as more data are available,” they concluded.
The study was funded by the Duncan Family Institute, the Cancer Prevention Research Institute of Texas, and the National Institutes of Health. The authors reported having no conflicts of interest.
SOURCE: Fu S et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 30. doi: 10.1016/j.clml.2019.08.014.
In older patients with newly diagnosed mantle cell lymphoma (MCL), first-line therapy with rituximab- and bendamustine-based regimens significantly reduced 1-year mortality rates versus chemotherapy alone, according to a retrospective analysis.
“This study evaluated the comparative effectiveness of [rituximab, bortezomib, or bendamustine] in elderly patients newly diagnosed with MCL,” wrote Shuangshuang Fu, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in Clinical Lymphoma, Myeloma & Leukemia.
The researchers studied population-based data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. They identified all patients over age 65 years who received a new diagnosis of MCL between Jan. 1, 1999, and Dec. 31, 2013.
The study cohort included a total of 1,215 patients. Participants were classified into four different groups according to treatment regimen: chemotherapy alone, rituximab plus or minus chemotherapy, bendamustine plus or minus chemotherapy, and bortezomib plus or minus chemotherapy.
At 1-year follow-up, the team analyzed various mortality outcomes, including MCL-specific, all-cause, and noncancer mortality. The bortezomib results were not included in the primary analysis because of small sample size, according to the researchers.
After multivariable analysis, Dr. Fu and colleagues found that 1-year all-cause mortality rate was significantly lower for patients receiving rituximab-based regimens, compared with chemotherapy alone (hazard ratio, 0.38; 95% confidence interval, 0.25-0.59). There was a similar decline for MCL-specific mortality (HR, 0.38; 95% CI, 0.24-0.60).
The 1-year MCL-specific mortality was also significantly reduced in the bendamustine group, compared with chemotherapy alone (HR, 0.49; 95% CI, 0.24-0.99).
“Our findings comparing rituximab with chemotherapy alone further confirmed the benefit of adding rituximab to chemotherapy in newly diagnosed older MCL patients,” they wrote.
The researchers acknowledged that a key limitation of the study was the observational design. As a result, selection bias and unmeasured confounding could have influenced the results.
“Future studies evaluating the comparative effectiveness of those newly approved novel agents for MCL patients were warranted as more data are available,” they concluded.
The study was funded by the Duncan Family Institute, the Cancer Prevention Research Institute of Texas, and the National Institutes of Health. The authors reported having no conflicts of interest.
SOURCE: Fu S et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 30. doi: 10.1016/j.clml.2019.08.014.
In older patients with newly diagnosed mantle cell lymphoma (MCL), first-line therapy with rituximab- and bendamustine-based regimens significantly reduced 1-year mortality rates versus chemotherapy alone, according to a retrospective analysis.
“This study evaluated the comparative effectiveness of [rituximab, bortezomib, or bendamustine] in elderly patients newly diagnosed with MCL,” wrote Shuangshuang Fu, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in Clinical Lymphoma, Myeloma & Leukemia.
The researchers studied population-based data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. They identified all patients over age 65 years who received a new diagnosis of MCL between Jan. 1, 1999, and Dec. 31, 2013.
The study cohort included a total of 1,215 patients. Participants were classified into four different groups according to treatment regimen: chemotherapy alone, rituximab plus or minus chemotherapy, bendamustine plus or minus chemotherapy, and bortezomib plus or minus chemotherapy.
At 1-year follow-up, the team analyzed various mortality outcomes, including MCL-specific, all-cause, and noncancer mortality. The bortezomib results were not included in the primary analysis because of small sample size, according to the researchers.
After multivariable analysis, Dr. Fu and colleagues found that 1-year all-cause mortality rate was significantly lower for patients receiving rituximab-based regimens, compared with chemotherapy alone (hazard ratio, 0.38; 95% confidence interval, 0.25-0.59). There was a similar decline for MCL-specific mortality (HR, 0.38; 95% CI, 0.24-0.60).
The 1-year MCL-specific mortality was also significantly reduced in the bendamustine group, compared with chemotherapy alone (HR, 0.49; 95% CI, 0.24-0.99).
“Our findings comparing rituximab with chemotherapy alone further confirmed the benefit of adding rituximab to chemotherapy in newly diagnosed older MCL patients,” they wrote.
The researchers acknowledged that a key limitation of the study was the observational design. As a result, selection bias and unmeasured confounding could have influenced the results.
“Future studies evaluating the comparative effectiveness of those newly approved novel agents for MCL patients were warranted as more data are available,” they concluded.
The study was funded by the Duncan Family Institute, the Cancer Prevention Research Institute of Texas, and the National Institutes of Health. The authors reported having no conflicts of interest.
SOURCE: Fu S et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 30. doi: 10.1016/j.clml.2019.08.014.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Progressive myeloma after induction? Go straight to transplant
Patients with multiple myeloma who don’t respond to induction therapy may be better off advancing straight to autologous stem cell therapy, rather than undergoing salvage therapy before transplant, according to findings of an analysis that included both real-world and clinical trial patients.
Joanna Blocka, MD, of the University Hospital of Heidelberg (Germany) and colleagues found similar progression-free and overall survival rates for patients who had progressive disease and underwent autologous stem cell therapy (ASCT), compared with patients who underwent salvage therapy and improved to at least stable disease before proceeding to transplant. The findings were published in Leukemia & Lymphoma.
The real-world analysis included 1,599 patients with multiple myeloma who had undergone ASCT between 1991 and 2016. More than half of the patients (58%) were not enrolled in clinical trials. The remainder were split between the German-Speaking Myeloma Multicenter Group (GMMG)-HD3 and GMMG-HD4 trials, which compared various induction regimens.
Just 23 patients in the analysis received salvage therapy because of progressive disease and deepened their response before ASCT. Of these patients, 12 received novel agents in induction therapy and 11 received older medications.
Looking across all 1,599 patients, 5.3% achieved complete remission before first ASCT. Most patients (71.8%) achieved partial remission, 9.7% had a minimal response, and 5.7% had stable disease. A group of 120 patients (7.5%) progressed between the last course of induction and ASCT.
The researchers compared the progression-free and overall survival rates of patients with progressive disease versus those who had stable disease or better before their first transplant. Both univariable and multivariable analysis showed no statistically significant differences in either survival outcome between the two groups.
In the multivariable analysis, there was a hazard ratio of 1.23 (95% confidence interval, 0.98-1.56) for progression-free survival for patients with progressive disease versus those who responded to induction therapy. Similarly, the HR for overall survival between the two groups was 1.24 (95% CI, 0.93-1.65).
The researchers also analyzed the groups based on whether they received novel or older agents during induction.
Patients with progressive disease who received novel agents had significantly worse progression-free survival (22.2 months), compared with patients who responded to treatment with novel agents (22.2 months vs. 29.1 months; P = .03). The same trend was seen with overall survival in these groups (54.4 months vs. 97.5 months; P less than .001).
Rates of survival were similar for patients with progressive disease and responders who had received older medications at induction.
“This might be explained by a prognostically disadvantageous disease biology in patients nonresponsive to novel agents,” the researchers wrote.
The researchers also compared survival outcomes for the 120 patients who underwent ASCT with progressive disease versus the 23 patients who received salvage therapy and improved their response to at least stable disease before transplant. Univariable analysis showed that salvage patients actually did worse than those with progressive disease who proceeded straight to transplant – 12.1 months versus 22.9 months of progression-free survival (P = .04) and 33.1 versus 69.5 months of overall survival (P = .08). But on multivariable analysis, there was no significant difference between the two groups for progression-free survival (HR, 0.71; 95% CI, 0.28-1.80; P = .5) or overall survival (HR, 0.77; 95% CI, 0.30-1.95; P = .6). The use of novel agents did not appear to affect the survival outcomes in these patients.
The worse outcomes seen among salvage patients observed in univariable analysis “might be due to a cumulative toxic effect of salvage therapy,” the researchers suggested. “An alternative explanation could be that the patients who were offered salvage therapy might have had more aggressive disease than those who did not undergo salvage therapy.”
Dr. Blocka reported having no relevant financial disclosures. Other coauthors reported relationships with Janssen, Amgen, Bristol-Myers Squibb, Celgene, and others.
SOURCE: Blocka J et al. Leuk Lymphoma. 2019 Aug 19. doi: 10.1080/10428194.2019.1646905.
Patients with multiple myeloma who don’t respond to induction therapy may be better off advancing straight to autologous stem cell therapy, rather than undergoing salvage therapy before transplant, according to findings of an analysis that included both real-world and clinical trial patients.
Joanna Blocka, MD, of the University Hospital of Heidelberg (Germany) and colleagues found similar progression-free and overall survival rates for patients who had progressive disease and underwent autologous stem cell therapy (ASCT), compared with patients who underwent salvage therapy and improved to at least stable disease before proceeding to transplant. The findings were published in Leukemia & Lymphoma.
The real-world analysis included 1,599 patients with multiple myeloma who had undergone ASCT between 1991 and 2016. More than half of the patients (58%) were not enrolled in clinical trials. The remainder were split between the German-Speaking Myeloma Multicenter Group (GMMG)-HD3 and GMMG-HD4 trials, which compared various induction regimens.
Just 23 patients in the analysis received salvage therapy because of progressive disease and deepened their response before ASCT. Of these patients, 12 received novel agents in induction therapy and 11 received older medications.
Looking across all 1,599 patients, 5.3% achieved complete remission before first ASCT. Most patients (71.8%) achieved partial remission, 9.7% had a minimal response, and 5.7% had stable disease. A group of 120 patients (7.5%) progressed between the last course of induction and ASCT.
The researchers compared the progression-free and overall survival rates of patients with progressive disease versus those who had stable disease or better before their first transplant. Both univariable and multivariable analysis showed no statistically significant differences in either survival outcome between the two groups.
In the multivariable analysis, there was a hazard ratio of 1.23 (95% confidence interval, 0.98-1.56) for progression-free survival for patients with progressive disease versus those who responded to induction therapy. Similarly, the HR for overall survival between the two groups was 1.24 (95% CI, 0.93-1.65).
The researchers also analyzed the groups based on whether they received novel or older agents during induction.
Patients with progressive disease who received novel agents had significantly worse progression-free survival (22.2 months), compared with patients who responded to treatment with novel agents (22.2 months vs. 29.1 months; P = .03). The same trend was seen with overall survival in these groups (54.4 months vs. 97.5 months; P less than .001).
Rates of survival were similar for patients with progressive disease and responders who had received older medications at induction.
“This might be explained by a prognostically disadvantageous disease biology in patients nonresponsive to novel agents,” the researchers wrote.
The researchers also compared survival outcomes for the 120 patients who underwent ASCT with progressive disease versus the 23 patients who received salvage therapy and improved their response to at least stable disease before transplant. Univariable analysis showed that salvage patients actually did worse than those with progressive disease who proceeded straight to transplant – 12.1 months versus 22.9 months of progression-free survival (P = .04) and 33.1 versus 69.5 months of overall survival (P = .08). But on multivariable analysis, there was no significant difference between the two groups for progression-free survival (HR, 0.71; 95% CI, 0.28-1.80; P = .5) or overall survival (HR, 0.77; 95% CI, 0.30-1.95; P = .6). The use of novel agents did not appear to affect the survival outcomes in these patients.
The worse outcomes seen among salvage patients observed in univariable analysis “might be due to a cumulative toxic effect of salvage therapy,” the researchers suggested. “An alternative explanation could be that the patients who were offered salvage therapy might have had more aggressive disease than those who did not undergo salvage therapy.”
Dr. Blocka reported having no relevant financial disclosures. Other coauthors reported relationships with Janssen, Amgen, Bristol-Myers Squibb, Celgene, and others.
SOURCE: Blocka J et al. Leuk Lymphoma. 2019 Aug 19. doi: 10.1080/10428194.2019.1646905.
Patients with multiple myeloma who don’t respond to induction therapy may be better off advancing straight to autologous stem cell therapy, rather than undergoing salvage therapy before transplant, according to findings of an analysis that included both real-world and clinical trial patients.
Joanna Blocka, MD, of the University Hospital of Heidelberg (Germany) and colleagues found similar progression-free and overall survival rates for patients who had progressive disease and underwent autologous stem cell therapy (ASCT), compared with patients who underwent salvage therapy and improved to at least stable disease before proceeding to transplant. The findings were published in Leukemia & Lymphoma.
The real-world analysis included 1,599 patients with multiple myeloma who had undergone ASCT between 1991 and 2016. More than half of the patients (58%) were not enrolled in clinical trials. The remainder were split between the German-Speaking Myeloma Multicenter Group (GMMG)-HD3 and GMMG-HD4 trials, which compared various induction regimens.
Just 23 patients in the analysis received salvage therapy because of progressive disease and deepened their response before ASCT. Of these patients, 12 received novel agents in induction therapy and 11 received older medications.
Looking across all 1,599 patients, 5.3% achieved complete remission before first ASCT. Most patients (71.8%) achieved partial remission, 9.7% had a minimal response, and 5.7% had stable disease. A group of 120 patients (7.5%) progressed between the last course of induction and ASCT.
The researchers compared the progression-free and overall survival rates of patients with progressive disease versus those who had stable disease or better before their first transplant. Both univariable and multivariable analysis showed no statistically significant differences in either survival outcome between the two groups.
In the multivariable analysis, there was a hazard ratio of 1.23 (95% confidence interval, 0.98-1.56) for progression-free survival for patients with progressive disease versus those who responded to induction therapy. Similarly, the HR for overall survival between the two groups was 1.24 (95% CI, 0.93-1.65).
The researchers also analyzed the groups based on whether they received novel or older agents during induction.
Patients with progressive disease who received novel agents had significantly worse progression-free survival (22.2 months), compared with patients who responded to treatment with novel agents (22.2 months vs. 29.1 months; P = .03). The same trend was seen with overall survival in these groups (54.4 months vs. 97.5 months; P less than .001).
Rates of survival were similar for patients with progressive disease and responders who had received older medications at induction.
“This might be explained by a prognostically disadvantageous disease biology in patients nonresponsive to novel agents,” the researchers wrote.
The researchers also compared survival outcomes for the 120 patients who underwent ASCT with progressive disease versus the 23 patients who received salvage therapy and improved their response to at least stable disease before transplant. Univariable analysis showed that salvage patients actually did worse than those with progressive disease who proceeded straight to transplant – 12.1 months versus 22.9 months of progression-free survival (P = .04) and 33.1 versus 69.5 months of overall survival (P = .08). But on multivariable analysis, there was no significant difference between the two groups for progression-free survival (HR, 0.71; 95% CI, 0.28-1.80; P = .5) or overall survival (HR, 0.77; 95% CI, 0.30-1.95; P = .6). The use of novel agents did not appear to affect the survival outcomes in these patients.
The worse outcomes seen among salvage patients observed in univariable analysis “might be due to a cumulative toxic effect of salvage therapy,” the researchers suggested. “An alternative explanation could be that the patients who were offered salvage therapy might have had more aggressive disease than those who did not undergo salvage therapy.”
Dr. Blocka reported having no relevant financial disclosures. Other coauthors reported relationships with Janssen, Amgen, Bristol-Myers Squibb, Celgene, and others.
SOURCE: Blocka J et al. Leuk Lymphoma. 2019 Aug 19. doi: 10.1080/10428194.2019.1646905.
FROM LEUKEMIA & LYMPHOMA
Key clinical point:
Major finding: There was no difference between patients with progressive disease who went straight to ASCT and patients who received salvage therapy, both in terms of progression-free survival (hazard ratio, 0.71; 95% confidence interval, 0.28-1.80; P = .5) and overall survival (HR, 0.77; 95% CI, 0.30-1.95; P = .6).
Study details: An analysis of 1,599 patients with multiple myeloma who underwent ASCT. A subanalysis compared 120 patients with progressive disease before ASCT with 23 patients who received salvage treatment before ASCT.
Disclosures: Dr. Blocka reported having no relevant financial disclosures. Other coauthors reported relationships with Janssen, Amgen, Bristol-Myers Squibb, Celgene, and others.
Source: Blocka J et al. Leuk Lymphoma. 2019 Aug 19. doi: 10.1080/10428194.2019.1646905.
CK doesn’t seem to affect OS in CLL patients taking idelalisib
The presence of complex karyotype (CK) does not affect survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who are treated with idelalisib, according to a new analysis.
Researchers analyzed data from two clinical trials of idelalisib, given alone or in combination with rituximab, and found no significant difference in overall survival (OS) between patients with and without CK.
Karl-Anton Kreuzer, MD, of the University of Cologne (Germany), and colleagues described these findings in a letter to Leukemia.
The researchers evaluated patients with previously treated CLL who were enrolled in a phase 3 trial and received either idelalisib plus rituximab or rituximab plus placebo. Patients from either treatment arm could enroll in an extension study of idelalisib monotherapy.
There were 220 patients randomized to idelalisib plus rituximab (n = 110) or placebo plus rituximab (n = 110) in the primary study, and 161 of these patients were enrolled in the extension study.
The final analysis included 120 patients who were successfully karyotyped – 63 from the idelalisib-rituximab arm and 57 from the placebo-rituximab arm. Less than half of patients in each arm were CK-positive – 41% (26/63) of the idelalisib arm and 42% (24/57) of the placebo arm.
The researchers wrote that baseline characteristics were “mostly balanced” between the CK-positive and CK-negative groups in each treatment arm. The only significant difference was that fewer CK-positive patients in the placebo arm had a creatinine clearance of 30-59 mL/min (P = .0324).
Results
There were no significant differences in outcomes between CK-positive and CK-negative patients who received idelalisib and rituximab. The overall response rate was 81% in CK-positive patients and 89% in CK-negative patients (P = .3509). The median progression-free survival was 20.9 months and 19.4 months, respectively (P = .5848).
The median OS was 28.3 months in the CK-positive group and 49.7 months in the CK-negative group (P = .2099). The copresence of CK and del(17p), TP53 mutation, or del(11q) didn’t significantly affect OS, the researchers noted.
Among all CK-positive patients, the median OS was 28.3 months in the idelalisib-rituximab arm and 9.2 months in the placebo-rituximab arm (P = .0412).
“Our analysis suggests that CK-positive patients treated with idelalisib/rituximab did not exhibit a significantly shortened survival compared with those who were CK negative,” the researchers wrote. “In addition, the primary beneficial effect of adding idelalisib to rituximab treatment in [relapsed/refractory] CLL patients with CK was reflected in OS prolongation compared to those who received only rituximab.”
The researchers noted that this study has limitations, so prospective clinical trials are needed to guide treatment of patients with relapsed/refractory CLL and CK.
Both trials of idelalisib were sponsored by Gilead. The researchers reported relationships, including employment, with Gilead and other companies. They also disclosed funding from the German government and from nonprofit organizations in Germany.
SOURCE: Kreuzer K-A et al. Leukemia. 2019 Aug 19. doi: 10.1038/s41375-019-0533-6.
The presence of complex karyotype (CK) does not affect survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who are treated with idelalisib, according to a new analysis.
Researchers analyzed data from two clinical trials of idelalisib, given alone or in combination with rituximab, and found no significant difference in overall survival (OS) between patients with and without CK.
Karl-Anton Kreuzer, MD, of the University of Cologne (Germany), and colleagues described these findings in a letter to Leukemia.
The researchers evaluated patients with previously treated CLL who were enrolled in a phase 3 trial and received either idelalisib plus rituximab or rituximab plus placebo. Patients from either treatment arm could enroll in an extension study of idelalisib monotherapy.
There were 220 patients randomized to idelalisib plus rituximab (n = 110) or placebo plus rituximab (n = 110) in the primary study, and 161 of these patients were enrolled in the extension study.
The final analysis included 120 patients who were successfully karyotyped – 63 from the idelalisib-rituximab arm and 57 from the placebo-rituximab arm. Less than half of patients in each arm were CK-positive – 41% (26/63) of the idelalisib arm and 42% (24/57) of the placebo arm.
The researchers wrote that baseline characteristics were “mostly balanced” between the CK-positive and CK-negative groups in each treatment arm. The only significant difference was that fewer CK-positive patients in the placebo arm had a creatinine clearance of 30-59 mL/min (P = .0324).
Results
There were no significant differences in outcomes between CK-positive and CK-negative patients who received idelalisib and rituximab. The overall response rate was 81% in CK-positive patients and 89% in CK-negative patients (P = .3509). The median progression-free survival was 20.9 months and 19.4 months, respectively (P = .5848).
The median OS was 28.3 months in the CK-positive group and 49.7 months in the CK-negative group (P = .2099). The copresence of CK and del(17p), TP53 mutation, or del(11q) didn’t significantly affect OS, the researchers noted.
Among all CK-positive patients, the median OS was 28.3 months in the idelalisib-rituximab arm and 9.2 months in the placebo-rituximab arm (P = .0412).
“Our analysis suggests that CK-positive patients treated with idelalisib/rituximab did not exhibit a significantly shortened survival compared with those who were CK negative,” the researchers wrote. “In addition, the primary beneficial effect of adding idelalisib to rituximab treatment in [relapsed/refractory] CLL patients with CK was reflected in OS prolongation compared to those who received only rituximab.”
The researchers noted that this study has limitations, so prospective clinical trials are needed to guide treatment of patients with relapsed/refractory CLL and CK.
Both trials of idelalisib were sponsored by Gilead. The researchers reported relationships, including employment, with Gilead and other companies. They also disclosed funding from the German government and from nonprofit organizations in Germany.
SOURCE: Kreuzer K-A et al. Leukemia. 2019 Aug 19. doi: 10.1038/s41375-019-0533-6.
The presence of complex karyotype (CK) does not affect survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who are treated with idelalisib, according to a new analysis.
Researchers analyzed data from two clinical trials of idelalisib, given alone or in combination with rituximab, and found no significant difference in overall survival (OS) between patients with and without CK.
Karl-Anton Kreuzer, MD, of the University of Cologne (Germany), and colleagues described these findings in a letter to Leukemia.
The researchers evaluated patients with previously treated CLL who were enrolled in a phase 3 trial and received either idelalisib plus rituximab or rituximab plus placebo. Patients from either treatment arm could enroll in an extension study of idelalisib monotherapy.
There were 220 patients randomized to idelalisib plus rituximab (n = 110) or placebo plus rituximab (n = 110) in the primary study, and 161 of these patients were enrolled in the extension study.
The final analysis included 120 patients who were successfully karyotyped – 63 from the idelalisib-rituximab arm and 57 from the placebo-rituximab arm. Less than half of patients in each arm were CK-positive – 41% (26/63) of the idelalisib arm and 42% (24/57) of the placebo arm.
The researchers wrote that baseline characteristics were “mostly balanced” between the CK-positive and CK-negative groups in each treatment arm. The only significant difference was that fewer CK-positive patients in the placebo arm had a creatinine clearance of 30-59 mL/min (P = .0324).
Results
There were no significant differences in outcomes between CK-positive and CK-negative patients who received idelalisib and rituximab. The overall response rate was 81% in CK-positive patients and 89% in CK-negative patients (P = .3509). The median progression-free survival was 20.9 months and 19.4 months, respectively (P = .5848).
The median OS was 28.3 months in the CK-positive group and 49.7 months in the CK-negative group (P = .2099). The copresence of CK and del(17p), TP53 mutation, or del(11q) didn’t significantly affect OS, the researchers noted.
Among all CK-positive patients, the median OS was 28.3 months in the idelalisib-rituximab arm and 9.2 months in the placebo-rituximab arm (P = .0412).
“Our analysis suggests that CK-positive patients treated with idelalisib/rituximab did not exhibit a significantly shortened survival compared with those who were CK negative,” the researchers wrote. “In addition, the primary beneficial effect of adding idelalisib to rituximab treatment in [relapsed/refractory] CLL patients with CK was reflected in OS prolongation compared to those who received only rituximab.”
The researchers noted that this study has limitations, so prospective clinical trials are needed to guide treatment of patients with relapsed/refractory CLL and CK.
Both trials of idelalisib were sponsored by Gilead. The researchers reported relationships, including employment, with Gilead and other companies. They also disclosed funding from the German government and from nonprofit organizations in Germany.
SOURCE: Kreuzer K-A et al. Leukemia. 2019 Aug 19. doi: 10.1038/s41375-019-0533-6.
FROM LEUKEMIA
Mitapivat elicits positive response in pyruvate kinase deficiency
Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.
After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.
“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.
The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.
The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.
Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.
At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).
Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.
“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.
With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).
“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.
Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.
Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.
After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.
“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.
The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.
The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.
Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.
At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).
Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.
“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.
With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).
“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.
Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.
Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.
After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.
“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.
The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.
The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.
Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.
At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).
Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.
“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.
With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).
“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.
Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Major finding: At 24 weeks, 50% of patients experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL).
Study details: A phase 2 study of 52 patients with pyruvate kinase deficiency.
Disclosures: Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
Source: Grace RF et al. N Engl J Med. 2019;381:933-44.