Lymphoma & Plasma Cell Disorders

follicular lymphoma

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has recommended orphan designation for G100 for the treatment of follicular lymphoma (FL).

G100 contains the synthetic small molecule toll-like receptor-4 agonist glucopyranosyl lipid A.

G100 works by activating innate and adaptive immunity in the tumor microenvironment to generate an immune response against the tumor’s pre-existing antigens.

Clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The induction of local and systemic immune responses has been shown in preclinical studies to result in local and abscopal tumor control.

Immune Design, the company developing G100, is currently evaluating G100 plus local radiation, with or without pembrolizumab, in a phase 1/2 trial of FL patients.

Results from this trial were presented at the 2017 ASCO Annual Meeting (abstract 7537). Nine patients who received G100 (3 patients each at the 5, 10, or 20 μg dose) with radiation (but not pembrolizumab) were evaluable for safety and efficacy.

The overall response rate was 44%, and all of these were partial responses (n=4). Thirty-three percent of patients had stable disease (n=3).

Among the responders, tumor regression ranged from 58% to 89%, which included up to 56% shrinkage of abscopal sites. Tumor biopsies showed increased inflammatory responses and T-cell infiltrates in abscopal tumors.

An additional 13 patients treated at the 10 μg dose were evaluable for safety.  There were no dose-limiting toxicities, serious adverse events (AEs), or grade 3/4 AEs observed.

Common AEs included injection site disorders, abdominal pain/discomfort, nausea, pruritus, and decrease in lymphocytes.

Immune Design said that, if this trial produces a sufficiently robust clinical benefit for patients, the company may pursue FL as the first indication for regulatory approval of G100.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

follicular lymphoma

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has recommended orphan designation for G100 for the treatment of follicular lymphoma (FL).

G100 contains the synthetic small molecule toll-like receptor-4 agonist glucopyranosyl lipid A.

G100 works by activating innate and adaptive immunity in the tumor microenvironment to generate an immune response against the tumor’s pre-existing antigens.

Clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The induction of local and systemic immune responses has been shown in preclinical studies to result in local and abscopal tumor control.

Immune Design, the company developing G100, is currently evaluating G100 plus local radiation, with or without pembrolizumab, in a phase 1/2 trial of FL patients.

Results from this trial were presented at the 2017 ASCO Annual Meeting (abstract 7537). Nine patients who received G100 (3 patients each at the 5, 10, or 20 μg dose) with radiation (but not pembrolizumab) were evaluable for safety and efficacy.

The overall response rate was 44%, and all of these were partial responses (n=4). Thirty-three percent of patients had stable disease (n=3).

Among the responders, tumor regression ranged from 58% to 89%, which included up to 56% shrinkage of abscopal sites. Tumor biopsies showed increased inflammatory responses and T-cell infiltrates in abscopal tumors.

An additional 13 patients treated at the 10 μg dose were evaluable for safety.  There were no dose-limiting toxicities, serious adverse events (AEs), or grade 3/4 AEs observed.

Common AEs included injection site disorders, abdominal pain/discomfort, nausea, pruritus, and decrease in lymphocytes.

Immune Design said that, if this trial produces a sufficiently robust clinical benefit for patients, the company may pursue FL as the first indication for regulatory approval of G100.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

follicular lymphoma

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has recommended orphan designation for G100 for the treatment of follicular lymphoma (FL).

G100 contains the synthetic small molecule toll-like receptor-4 agonist glucopyranosyl lipid A.

G100 works by activating innate and adaptive immunity in the tumor microenvironment to generate an immune response against the tumor’s pre-existing antigens.

Clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The induction of local and systemic immune responses has been shown in preclinical studies to result in local and abscopal tumor control.

Immune Design, the company developing G100, is currently evaluating G100 plus local radiation, with or without pembrolizumab, in a phase 1/2 trial of FL patients.

Results from this trial were presented at the 2017 ASCO Annual Meeting (abstract 7537). Nine patients who received G100 (3 patients each at the 5, 10, or 20 μg dose) with radiation (but not pembrolizumab) were evaluable for safety and efficacy.

The overall response rate was 44%, and all of these were partial responses (n=4). Thirty-three percent of patients had stable disease (n=3).

Among the responders, tumor regression ranged from 58% to 89%, which included up to 56% shrinkage of abscopal sites. Tumor biopsies showed increased inflammatory responses and T-cell infiltrates in abscopal tumors.

An additional 13 patients treated at the 10 μg dose were evaluable for safety.  There were no dose-limiting toxicities, serious adverse events (AEs), or grade 3/4 AEs observed.

Common AEs included injection site disorders, abdominal pain/discomfort, nausea, pruritus, and decrease in lymphocytes.

Immune Design said that, if this trial produces a sufficiently robust clinical benefit for patients, the company may pursue FL as the first indication for regulatory approval of G100.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

In elderly patients with aggressive B-cell lymphomas who experience treatment failure after CHOP or rituximab-CHOP (R-CHOP), the outcomes of subsequent salvage therapy were improved when rituximab was included, results of a retrospective analysis suggest.

“Survival after rituximab-containing salvage therapy was better in all patient groups, supporting the repeated administration of rituximab to all patients needing salvage therapy,” wrote investigator Bertram Glass, MD, of the department of hematology and stem cell transplantation at Helios Klinikum Berlin-Buch, Berlin, and his coauthors (Ann Oncol. 2017 Oct 6. doi: 10.1093/annonc/mdx556).

Dr. Glass and colleagues reviewed data from the randomized RICOVER-60 trial, which included 1,222 patients aged 61-80 years with aggressive B-cell lymphomas who received CHOP or R-CHOP for six or eight cycles. Based on survival outcomes, six cycles of R-CHOP every 2 weeks should be the preferred regimen, investigators wrote when the study results were published in 2008 (Lancet Oncol. 2008;9[2]:105-16. doi: 10.1016/S1470-2045(08)70002-0).

Of 1,222 patients in the RICOVER-60 trial, 301 (24.6%) had treatment failure, of whom 297 could be included in the present analysis.

Rituximab, included in salvage therapy for 57.4% of those evaluable patients, was found to improve the 2-year survival rate from 20.7% to 46.8% (P less than .001), Dr. Glass and his coinvestigators reported.

The benefit of rituximab in the salvage setting was apparent regardless of whether patients received R-CHOP or CHOP as part of their initial therapy in RICOVER-60, they added.

Among patients who had received CHOP as first-line therapy, 2-year overall survival was 49.6% for those who received rituximab in the salvage setting, compared with 19.1% for those who did not (P less than .001), according to the published data. Likewise, in the initial R-CHOP group, 2-year overall survival was 33.1% for rituximab in salvage and 22.5% for no rituximab in salvage (P = .034).

The investigators also looked for differences in prognosis according to specific patient characteristics, including presence of MYC rearrangements and MYC expression by immunohistochemistry.

In patients with MYC translocation at diagnosis, use of rituximab reduced risk of initial treatment failure from 58.8% to 26.3%, according to the investigators. After treatment failure, patients who initially received CHOP had significantly improved 2-year survival if they had MYC translocations or negative MYC immunohistochemistry, though no such association was found for patients who initially received R-CHOP, they wrote.

Dr. Glass and colleagues concluded that new treatment strategies are needed.

“Overall, the outcome of second-line treatment of elderly patients with refractory and relapsed aggressive B-cell lymphoma is disappointing and worse than in younger patients regardless of the modality chosen,” they wrote. “New drugs and treatment modalities with the potential to change the dismal outlook for elderly patients with aggressive B-cell lymphomas are eagerly awaited.”

Dr. Glass and several coauthors reported honoraria, research funding, and consultancies with Roche.

In elderly patients with aggressive B-cell lymphomas who experience treatment failure after CHOP or rituximab-CHOP (R-CHOP), the outcomes of subsequent salvage therapy were improved when rituximab was included, results of a retrospective analysis suggest.

“Survival after rituximab-containing salvage therapy was better in all patient groups, supporting the repeated administration of rituximab to all patients needing salvage therapy,” wrote investigator Bertram Glass, MD, of the department of hematology and stem cell transplantation at Helios Klinikum Berlin-Buch, Berlin, and his coauthors (Ann Oncol. 2017 Oct 6. doi: 10.1093/annonc/mdx556).

Dr. Glass and colleagues reviewed data from the randomized RICOVER-60 trial, which included 1,222 patients aged 61-80 years with aggressive B-cell lymphomas who received CHOP or R-CHOP for six or eight cycles. Based on survival outcomes, six cycles of R-CHOP every 2 weeks should be the preferred regimen, investigators wrote when the study results were published in 2008 (Lancet Oncol. 2008;9[2]:105-16. doi: 10.1016/S1470-2045(08)70002-0).

Of 1,222 patients in the RICOVER-60 trial, 301 (24.6%) had treatment failure, of whom 297 could be included in the present analysis.

Rituximab, included in salvage therapy for 57.4% of those evaluable patients, was found to improve the 2-year survival rate from 20.7% to 46.8% (P less than .001), Dr. Glass and his coinvestigators reported.

The benefit of rituximab in the salvage setting was apparent regardless of whether patients received R-CHOP or CHOP as part of their initial therapy in RICOVER-60, they added.

Among patients who had received CHOP as first-line therapy, 2-year overall survival was 49.6% for those who received rituximab in the salvage setting, compared with 19.1% for those who did not (P less than .001), according to the published data. Likewise, in the initial R-CHOP group, 2-year overall survival was 33.1% for rituximab in salvage and 22.5% for no rituximab in salvage (P = .034).

The investigators also looked for differences in prognosis according to specific patient characteristics, including presence of MYC rearrangements and MYC expression by immunohistochemistry.

In patients with MYC translocation at diagnosis, use of rituximab reduced risk of initial treatment failure from 58.8% to 26.3%, according to the investigators. After treatment failure, patients who initially received CHOP had significantly improved 2-year survival if they had MYC translocations or negative MYC immunohistochemistry, though no such association was found for patients who initially received R-CHOP, they wrote.

Dr. Glass and colleagues concluded that new treatment strategies are needed.

“Overall, the outcome of second-line treatment of elderly patients with refractory and relapsed aggressive B-cell lymphoma is disappointing and worse than in younger patients regardless of the modality chosen,” they wrote. “New drugs and treatment modalities with the potential to change the dismal outlook for elderly patients with aggressive B-cell lymphomas are eagerly awaited.”

Dr. Glass and several coauthors reported honoraria, research funding, and consultancies with Roche.

In elderly patients with aggressive B-cell lymphomas who experience treatment failure after CHOP or rituximab-CHOP (R-CHOP), the outcomes of subsequent salvage therapy were improved when rituximab was included, results of a retrospective analysis suggest.

“Survival after rituximab-containing salvage therapy was better in all patient groups, supporting the repeated administration of rituximab to all patients needing salvage therapy,” wrote investigator Bertram Glass, MD, of the department of hematology and stem cell transplantation at Helios Klinikum Berlin-Buch, Berlin, and his coauthors (Ann Oncol. 2017 Oct 6. doi: 10.1093/annonc/mdx556).

Dr. Glass and colleagues reviewed data from the randomized RICOVER-60 trial, which included 1,222 patients aged 61-80 years with aggressive B-cell lymphomas who received CHOP or R-CHOP for six or eight cycles. Based on survival outcomes, six cycles of R-CHOP every 2 weeks should be the preferred regimen, investigators wrote when the study results were published in 2008 (Lancet Oncol. 2008;9[2]:105-16. doi: 10.1016/S1470-2045(08)70002-0).

Of 1,222 patients in the RICOVER-60 trial, 301 (24.6%) had treatment failure, of whom 297 could be included in the present analysis.

Rituximab, included in salvage therapy for 57.4% of those evaluable patients, was found to improve the 2-year survival rate from 20.7% to 46.8% (P less than .001), Dr. Glass and his coinvestigators reported.

The benefit of rituximab in the salvage setting was apparent regardless of whether patients received R-CHOP or CHOP as part of their initial therapy in RICOVER-60, they added.

Among patients who had received CHOP as first-line therapy, 2-year overall survival was 49.6% for those who received rituximab in the salvage setting, compared with 19.1% for those who did not (P less than .001), according to the published data. Likewise, in the initial R-CHOP group, 2-year overall survival was 33.1% for rituximab in salvage and 22.5% for no rituximab in salvage (P = .034).

The investigators also looked for differences in prognosis according to specific patient characteristics, including presence of MYC rearrangements and MYC expression by immunohistochemistry.

In patients with MYC translocation at diagnosis, use of rituximab reduced risk of initial treatment failure from 58.8% to 26.3%, according to the investigators. After treatment failure, patients who initially received CHOP had significantly improved 2-year survival if they had MYC translocations or negative MYC immunohistochemistry, though no such association was found for patients who initially received R-CHOP, they wrote.

Dr. Glass and colleagues concluded that new treatment strategies are needed.

“Overall, the outcome of second-line treatment of elderly patients with refractory and relapsed aggressive B-cell lymphoma is disappointing and worse than in younger patients regardless of the modality chosen,” they wrote. “New drugs and treatment modalities with the potential to change the dismal outlook for elderly patients with aggressive B-cell lymphomas are eagerly awaited.”

Dr. Glass and several coauthors reported honoraria, research funding, and consultancies with Roche.

As preparation for autologous stem cell transplantation, total-body irradiation was as safe and effective as chemotherapy conditioning, in a retrospective analysis of mantle cell lymphoma patient records.

“Our data suggest that both TBI [total-body irradiation] and BEAM [carmustine, etoposide, cytarabine, and melphalan]-based conditioning regimens remain viable conditioning options for MCL patients undergoing ASCT [autologous stem cell transplantation],” wrote Yolanda D. Tseng, MD, of the University of Washington, Seattle, and her coinvestigators.

Progression-free survival, the primary outcome, was greater at 5 years’ follow-up in 43 TBI patients (66%) than in the 32 chemotherapy-conditioned patients (52%), but the difference did not reach statistical significance. Overall survival followed a similar pattern: TBI patients’ overall survival at 5 years was 82%, compared with 68% in the TBI patients, but this difference also lacked significance (Biol Blood Marrow Transplant. 2017 Oct 20; doi: 10.1016/j.bbmt.2017.10.029).

Safety outcomes, including early toxicity, nonrelapse mortality, and secondary malignancies, also were similar between groups.

For the analysis, Dr. Tseng and her colleagues reviewed the records of 75 consecutive adult patients treated during 2001-2011 with ASCT at the Fred Hutchinson Cancer Research Center in Seattle. All underwent conditioning with either myeloablative TBI or a BEAM-based regimen.

Most of the patients had chemosensitive disease (97%), and nearly all received rituximab prior to ASCT.

Prior studies have shown that TBI can be at least as effective as chemotherapy conditioning, but none have looked at toxicity. These results indicate that either approach remains viable for patients undergoing ASCT for MCL, Dr. Tseng and her colleagues concluded.

No disclosures were reported.

chackett@frontlinemedcom.com

As preparation for autologous stem cell transplantation, total-body irradiation was as safe and effective as chemotherapy conditioning, in a retrospective analysis of mantle cell lymphoma patient records.

“Our data suggest that both TBI [total-body irradiation] and BEAM [carmustine, etoposide, cytarabine, and melphalan]-based conditioning regimens remain viable conditioning options for MCL patients undergoing ASCT [autologous stem cell transplantation],” wrote Yolanda D. Tseng, MD, of the University of Washington, Seattle, and her coinvestigators.

Progression-free survival, the primary outcome, was greater at 5 years’ follow-up in 43 TBI patients (66%) than in the 32 chemotherapy-conditioned patients (52%), but the difference did not reach statistical significance. Overall survival followed a similar pattern: TBI patients’ overall survival at 5 years was 82%, compared with 68% in the TBI patients, but this difference also lacked significance (Biol Blood Marrow Transplant. 2017 Oct 20; doi: 10.1016/j.bbmt.2017.10.029).

Safety outcomes, including early toxicity, nonrelapse mortality, and secondary malignancies, also were similar between groups.

For the analysis, Dr. Tseng and her colleagues reviewed the records of 75 consecutive adult patients treated during 2001-2011 with ASCT at the Fred Hutchinson Cancer Research Center in Seattle. All underwent conditioning with either myeloablative TBI or a BEAM-based regimen.

Most of the patients had chemosensitive disease (97%), and nearly all received rituximab prior to ASCT.

Prior studies have shown that TBI can be at least as effective as chemotherapy conditioning, but none have looked at toxicity. These results indicate that either approach remains viable for patients undergoing ASCT for MCL, Dr. Tseng and her colleagues concluded.

No disclosures were reported.

chackett@frontlinemedcom.com

As preparation for autologous stem cell transplantation, total-body irradiation was as safe and effective as chemotherapy conditioning, in a retrospective analysis of mantle cell lymphoma patient records.

“Our data suggest that both TBI [total-body irradiation] and BEAM [carmustine, etoposide, cytarabine, and melphalan]-based conditioning regimens remain viable conditioning options for MCL patients undergoing ASCT [autologous stem cell transplantation],” wrote Yolanda D. Tseng, MD, of the University of Washington, Seattle, and her coinvestigators.

Progression-free survival, the primary outcome, was greater at 5 years’ follow-up in 43 TBI patients (66%) than in the 32 chemotherapy-conditioned patients (52%), but the difference did not reach statistical significance. Overall survival followed a similar pattern: TBI patients’ overall survival at 5 years was 82%, compared with 68% in the TBI patients, but this difference also lacked significance (Biol Blood Marrow Transplant. 2017 Oct 20; doi: 10.1016/j.bbmt.2017.10.029).

Safety outcomes, including early toxicity, nonrelapse mortality, and secondary malignancies, also were similar between groups.

For the analysis, Dr. Tseng and her colleagues reviewed the records of 75 consecutive adult patients treated during 2001-2011 with ASCT at the Fred Hutchinson Cancer Research Center in Seattle. All underwent conditioning with either myeloablative TBI or a BEAM-based regimen.

Most of the patients had chemosensitive disease (97%), and nearly all received rituximab prior to ASCT.

Prior studies have shown that TBI can be at least as effective as chemotherapy conditioning, but none have looked at toxicity. These results indicate that either approach remains viable for patients undergoing ASCT for MCL, Dr. Tseng and her colleagues concluded.

No disclosures were reported.

chackett@frontlinemedcom.com

Micrograph showing DLBCL

A new assay may help improve the diagnosis and treatment of diffuse large B-cell lymphoma (DLBCL), according to researchers.

The gene expression signature assay can be used to classify subtypes of DLBCL and may enhance disease management by helping to match tumors with the appropriate targeted therapy.

Researchers described the assay in the Journal of Molecular Diagnostics.

The assay is a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA).

It can simultaneously evaluate the expression of 21 markers, allowing differentiation of the 3 subtypes of DLBCL—germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL)—as well as other individualized disease characteristics, such as Epstein-Barr infection status.

Researchers used the RT-MLPA assay to test 150 samples from DLBCL patients. Forty-two percent of the samples were the ABC subtype, 37% the GCB subtype, and 10% molecular PMBL. Eleven percent of the samples could not be classified.

Overall, the RT-MLPA assay correctly assigned 85.0% of the cases into the expected subtypes, compared to 78.8% of samples assigned via immunohistochemistry.

The RT-MLPA assay was also able to detect the MYD88 L265P mutation, one of the most common genetic abnormalities found in ABC DLBCLs. This information can influence treatment, since the presence of the mutation is thought to be predictive of ibrutinib sensitivity.

The researchers said RT-MLPA is a robust, efficient, rapid, and cost-effective alternative to current methods used in the clinic to establish the cell-of-origin classification of DLBCLs.

RT-MLPA requires only common laboratory equipment and can be applied to formalin-fixed, paraffin-embedded samples. Other types of diagnostic methods may not provide the level of detail needed and may also be limited by poor reproducibility and lack of adaptability to routine use in standard laboratories.

“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said study author Philippe Ruminy, PhD, of the Henri Becquerel Cancer Treatment Center, INSERM U1245 in Rouen, France.

“It is our hope that the assay we have developed, which addresses an important recommendation of the recent WHO classifications, will contribute to better management of these tumors and improved patient outcomes.”

Micrograph showing DLBCL

A new assay may help improve the diagnosis and treatment of diffuse large B-cell lymphoma (DLBCL), according to researchers.

The gene expression signature assay can be used to classify subtypes of DLBCL and may enhance disease management by helping to match tumors with the appropriate targeted therapy.

Researchers described the assay in the Journal of Molecular Diagnostics.

The assay is a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA).

It can simultaneously evaluate the expression of 21 markers, allowing differentiation of the 3 subtypes of DLBCL—germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL)—as well as other individualized disease characteristics, such as Epstein-Barr infection status.

Researchers used the RT-MLPA assay to test 150 samples from DLBCL patients. Forty-two percent of the samples were the ABC subtype, 37% the GCB subtype, and 10% molecular PMBL. Eleven percent of the samples could not be classified.

Overall, the RT-MLPA assay correctly assigned 85.0% of the cases into the expected subtypes, compared to 78.8% of samples assigned via immunohistochemistry.

The RT-MLPA assay was also able to detect the MYD88 L265P mutation, one of the most common genetic abnormalities found in ABC DLBCLs. This information can influence treatment, since the presence of the mutation is thought to be predictive of ibrutinib sensitivity.

The researchers said RT-MLPA is a robust, efficient, rapid, and cost-effective alternative to current methods used in the clinic to establish the cell-of-origin classification of DLBCLs.

RT-MLPA requires only common laboratory equipment and can be applied to formalin-fixed, paraffin-embedded samples. Other types of diagnostic methods may not provide the level of detail needed and may also be limited by poor reproducibility and lack of adaptability to routine use in standard laboratories.

“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said study author Philippe Ruminy, PhD, of the Henri Becquerel Cancer Treatment Center, INSERM U1245 in Rouen, France.

“It is our hope that the assay we have developed, which addresses an important recommendation of the recent WHO classifications, will contribute to better management of these tumors and improved patient outcomes.”

Micrograph showing DLBCL

A new assay may help improve the diagnosis and treatment of diffuse large B-cell lymphoma (DLBCL), according to researchers.

The gene expression signature assay can be used to classify subtypes of DLBCL and may enhance disease management by helping to match tumors with the appropriate targeted therapy.

Researchers described the assay in the Journal of Molecular Diagnostics.

The assay is a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA).

It can simultaneously evaluate the expression of 21 markers, allowing differentiation of the 3 subtypes of DLBCL—germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL)—as well as other individualized disease characteristics, such as Epstein-Barr infection status.

Researchers used the RT-MLPA assay to test 150 samples from DLBCL patients. Forty-two percent of the samples were the ABC subtype, 37% the GCB subtype, and 10% molecular PMBL. Eleven percent of the samples could not be classified.

Overall, the RT-MLPA assay correctly assigned 85.0% of the cases into the expected subtypes, compared to 78.8% of samples assigned via immunohistochemistry.

The RT-MLPA assay was also able to detect the MYD88 L265P mutation, one of the most common genetic abnormalities found in ABC DLBCLs. This information can influence treatment, since the presence of the mutation is thought to be predictive of ibrutinib sensitivity.

The researchers said RT-MLPA is a robust, efficient, rapid, and cost-effective alternative to current methods used in the clinic to establish the cell-of-origin classification of DLBCLs.

RT-MLPA requires only common laboratory equipment and can be applied to formalin-fixed, paraffin-embedded samples. Other types of diagnostic methods may not provide the level of detail needed and may also be limited by poor reproducibility and lack of adaptability to routine use in standard laboratories.

“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said study author Philippe Ruminy, PhD, of the Henri Becquerel Cancer Treatment Center, INSERM U1245 in Rouen, France.

“It is our hope that the assay we have developed, which addresses an important recommendation of the recent WHO classifications, will contribute to better management of these tumors and improved patient outcomes.”

Photo courtesy of FDA

Results of a systematic review suggest a need for more research and long-term follow-up of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

Although data suggest BIA-ALCL is likely associated with textured implants and may result from chronic inflammation, neither of these theories has been confirmed.

Furthermore, researchers have yet to establish optimal prognostic and treatment guidelines for BIA-ALCL.

Dino Ravnic, DO, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and his colleagues highlighted these areas of need in an article published in JAMA Surgery.

The team conducted a literature review to learn more about the development, risk factors, diagnosis, and treatment of BIA-ALCL. They reviewed data from 115 articles and 95 patients.

The researchers noted that the incidence of BIA-ALCL is unknown. The Association of Breast Surgery estimates an incidence of 1 in 300,000 breast implants, while the Australian Therapeutic Goods Administration estimates BIA-ALCL could affect between 1 in 1000 and 1 in 10,000 women with breast implants.

“We’re seeing that this cancer is likely very underreported, and, as more information on this type of cancer comes to light, the number of cases is likely to increase in the coming years,” Dr Ravnic said.

He and his colleagues noted that almost all documented cases of BIA-ALCL have been associated with textured implants. These implants rose in popularity in the 1990s, and the first case of BIA-ALCL was documented in 1997.

The researchers said that because they could find no incidents of BIA-ALCL prior to the introduction of textured implants, this suggests a causal relationship, but more research is needed to confirm this theory.

“We’re still exploring the exact causes, but according to current knowledge, this cancer only really started to appear after textured implants came on the market in the 1990s,” Dr Ravnic said.

“All manufacturers of textured implants have had cases linked to this type of lymphoma, and we haven’t seen cases linked to smooth implants. But, in many of these cases, the implant was removed without testing the surrounding fluid and tissue for lymphoma cells, so it’s difficult to definitively correlate the two.”

The researchers also said the evidence suggests BIA-ALCL may occur as a result of inflammation surrounding the breast implant, and tissue that grows into pores in the textured implant may prolong inflammation.

Chronic inflammation may lead to malignant transformation of T cells that are anaplastic lymphoma kinase-negative and CD30-positive.

The data also suggest BIA-ALCL tends to develop slowly. The mean time to BIA-ALCL presentation in the 95 patients analyzed was about 10 years after the patients received their implants.

The researchers said treatment of BIA-ALCL must include removal of the implant and surrounding capsule. However, patients with advanced disease—including a tumor mass (stage II), lymph node involvement (stage II/III), or distant disease (stage IV)—may require chemotherapy, radiotherapy, or both. Brentuximab vedotin has also been used.

Overall, the patients included in this review appeared to have a good prognosis, with only 5 patients experiencing disease recurrence and dying of BIA-ALCL.

However, the researchers noted that it was difficult to calculate the mean overall survival and disease-free survival of these patients due to a lack of data and inadequate follow-up.

Photo courtesy of FDA

Results of a systematic review suggest a need for more research and long-term follow-up of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

Although data suggest BIA-ALCL is likely associated with textured implants and may result from chronic inflammation, neither of these theories has been confirmed.

Furthermore, researchers have yet to establish optimal prognostic and treatment guidelines for BIA-ALCL.

Dino Ravnic, DO, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and his colleagues highlighted these areas of need in an article published in JAMA Surgery.

The team conducted a literature review to learn more about the development, risk factors, diagnosis, and treatment of BIA-ALCL. They reviewed data from 115 articles and 95 patients.

The researchers noted that the incidence of BIA-ALCL is unknown. The Association of Breast Surgery estimates an incidence of 1 in 300,000 breast implants, while the Australian Therapeutic Goods Administration estimates BIA-ALCL could affect between 1 in 1000 and 1 in 10,000 women with breast implants.

“We’re seeing that this cancer is likely very underreported, and, as more information on this type of cancer comes to light, the number of cases is likely to increase in the coming years,” Dr Ravnic said.

He and his colleagues noted that almost all documented cases of BIA-ALCL have been associated with textured implants. These implants rose in popularity in the 1990s, and the first case of BIA-ALCL was documented in 1997.

The researchers said that because they could find no incidents of BIA-ALCL prior to the introduction of textured implants, this suggests a causal relationship, but more research is needed to confirm this theory.

“We’re still exploring the exact causes, but according to current knowledge, this cancer only really started to appear after textured implants came on the market in the 1990s,” Dr Ravnic said.

“All manufacturers of textured implants have had cases linked to this type of lymphoma, and we haven’t seen cases linked to smooth implants. But, in many of these cases, the implant was removed without testing the surrounding fluid and tissue for lymphoma cells, so it’s difficult to definitively correlate the two.”

The researchers also said the evidence suggests BIA-ALCL may occur as a result of inflammation surrounding the breast implant, and tissue that grows into pores in the textured implant may prolong inflammation.

Chronic inflammation may lead to malignant transformation of T cells that are anaplastic lymphoma kinase-negative and CD30-positive.

The data also suggest BIA-ALCL tends to develop slowly. The mean time to BIA-ALCL presentation in the 95 patients analyzed was about 10 years after the patients received their implants.

The researchers said treatment of BIA-ALCL must include removal of the implant and surrounding capsule. However, patients with advanced disease—including a tumor mass (stage II), lymph node involvement (stage II/III), or distant disease (stage IV)—may require chemotherapy, radiotherapy, or both. Brentuximab vedotin has also been used.

Overall, the patients included in this review appeared to have a good prognosis, with only 5 patients experiencing disease recurrence and dying of BIA-ALCL.

However, the researchers noted that it was difficult to calculate the mean overall survival and disease-free survival of these patients due to a lack of data and inadequate follow-up.

Photo courtesy of FDA

Results of a systematic review suggest a need for more research and long-term follow-up of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

Although data suggest BIA-ALCL is likely associated with textured implants and may result from chronic inflammation, neither of these theories has been confirmed.

Furthermore, researchers have yet to establish optimal prognostic and treatment guidelines for BIA-ALCL.

Dino Ravnic, DO, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and his colleagues highlighted these areas of need in an article published in JAMA Surgery.

The team conducted a literature review to learn more about the development, risk factors, diagnosis, and treatment of BIA-ALCL. They reviewed data from 115 articles and 95 patients.

The researchers noted that the incidence of BIA-ALCL is unknown. The Association of Breast Surgery estimates an incidence of 1 in 300,000 breast implants, while the Australian Therapeutic Goods Administration estimates BIA-ALCL could affect between 1 in 1000 and 1 in 10,000 women with breast implants.

“We’re seeing that this cancer is likely very underreported, and, as more information on this type of cancer comes to light, the number of cases is likely to increase in the coming years,” Dr Ravnic said.

He and his colleagues noted that almost all documented cases of BIA-ALCL have been associated with textured implants. These implants rose in popularity in the 1990s, and the first case of BIA-ALCL was documented in 1997.

The researchers said that because they could find no incidents of BIA-ALCL prior to the introduction of textured implants, this suggests a causal relationship, but more research is needed to confirm this theory.

“We’re still exploring the exact causes, but according to current knowledge, this cancer only really started to appear after textured implants came on the market in the 1990s,” Dr Ravnic said.

“All manufacturers of textured implants have had cases linked to this type of lymphoma, and we haven’t seen cases linked to smooth implants. But, in many of these cases, the implant was removed without testing the surrounding fluid and tissue for lymphoma cells, so it’s difficult to definitively correlate the two.”

The researchers also said the evidence suggests BIA-ALCL may occur as a result of inflammation surrounding the breast implant, and tissue that grows into pores in the textured implant may prolong inflammation.

Chronic inflammation may lead to malignant transformation of T cells that are anaplastic lymphoma kinase-negative and CD30-positive.

The data also suggest BIA-ALCL tends to develop slowly. The mean time to BIA-ALCL presentation in the 95 patients analyzed was about 10 years after the patients received their implants.

The researchers said treatment of BIA-ALCL must include removal of the implant and surrounding capsule. However, patients with advanced disease—including a tumor mass (stage II), lymph node involvement (stage II/III), or distant disease (stage IV)—may require chemotherapy, radiotherapy, or both. Brentuximab vedotin has also been used.

Overall, the patients included in this review appeared to have a good prognosis, with only 5 patients experiencing disease recurrence and dying of BIA-ALCL.

However, the researchers noted that it was difficult to calculate the mean overall survival and disease-free survival of these patients due to a lack of data and inadequate follow-up.

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has approved axicabtagene ciloleucel (Yescarta™, formerly KTE-C19) for use in adults with relapsed or refractory large B-cell lymphoma who have received 2 or more lines of systemic therapy.

Axicabtagene ciloleucel is the first chimeric antigen receptor (CAR) T-cell therapy approved to treat lymphomas.

The approval encompasses diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and transformed follicular lymphoma.

Axicabtagene ciloleucel is not approved to treat primary central nervous system lymphoma.

The FDA’s approval of axicabtagene ciloleucel was based on results from the phase 2 ZUMA-1 trial. Updated results from this trial were presented at the AACR Annual Meeting 2017.

Risks

Axicabtagene ciloleucel has a Boxed Warning in its product label noting that the therapy can cause cytokine release syndrome (CRS) and neurologic toxicities. Full prescribing information for axicabtagene ciloleucel is available at https://www.yescarta.com/.

Because of the risk of CRS and neurologic toxicities, axicabtagene ciloleucel was approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use. The FDA is requiring that hospitals and clinics that dispense axicabtagene ciloleucel be specially certified.

As part of that certification, staff who prescribe, dispense, or administer axicabtagene ciloleucel are required to be trained to recognize and manage CRS and nervous system toxicities. In addition, patients must be informed of the potential serious side effects associated with axicabtagene ciloleucel and of the importance of promptly returning to the treatment site if side effects develop.

Additional information about the REMS program can be found at https://www.yescartarems.com/.

To further evaluate the long-term safety of axicabtagene ciloleucel, the FDA is requiring the manufacturer—Kite, a Gilead company—to conduct a post-marketing observational study of patients treated with axicabtagene ciloleucel.

Access and cost

The list price of axicabtagene ciloleucel is $373,000.

The product will be manufactured in Kite’s commercial manufacturing facility in El Segundo, California.

In 2017, Kite established a multi-disciplinary field team focused on providing education and logistics training for medical centers. Now, this team has provided final site certification to 16 centers, enabling them to make axicabtagene ciloleucel available to appropriate patients.

Kite is working to train staff at more than 30 additional centers, with an eventual target of 70 to 90 centers across the US. The latest information on authorized centers is available at https://www.yescarta.com/authorized-treatment-centers/.

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has approved axicabtagene ciloleucel (Yescarta™, formerly KTE-C19) for use in adults with relapsed or refractory large B-cell lymphoma who have received 2 or more lines of systemic therapy.

Axicabtagene ciloleucel is the first chimeric antigen receptor (CAR) T-cell therapy approved to treat lymphomas.

The approval encompasses diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and transformed follicular lymphoma.

Axicabtagene ciloleucel is not approved to treat primary central nervous system lymphoma.

The FDA’s approval of axicabtagene ciloleucel was based on results from the phase 2 ZUMA-1 trial. Updated results from this trial were presented at the AACR Annual Meeting 2017.

Risks

Axicabtagene ciloleucel has a Boxed Warning in its product label noting that the therapy can cause cytokine release syndrome (CRS) and neurologic toxicities. Full prescribing information for axicabtagene ciloleucel is available at https://www.yescarta.com/.

Because of the risk of CRS and neurologic toxicities, axicabtagene ciloleucel was approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use. The FDA is requiring that hospitals and clinics that dispense axicabtagene ciloleucel be specially certified.

As part of that certification, staff who prescribe, dispense, or administer axicabtagene ciloleucel are required to be trained to recognize and manage CRS and nervous system toxicities. In addition, patients must be informed of the potential serious side effects associated with axicabtagene ciloleucel and of the importance of promptly returning to the treatment site if side effects develop.

Additional information about the REMS program can be found at https://www.yescartarems.com/.

To further evaluate the long-term safety of axicabtagene ciloleucel, the FDA is requiring the manufacturer—Kite, a Gilead company—to conduct a post-marketing observational study of patients treated with axicabtagene ciloleucel.

Access and cost

The list price of axicabtagene ciloleucel is $373,000.

The product will be manufactured in Kite’s commercial manufacturing facility in El Segundo, California.

In 2017, Kite established a multi-disciplinary field team focused on providing education and logistics training for medical centers. Now, this team has provided final site certification to 16 centers, enabling them to make axicabtagene ciloleucel available to appropriate patients.

Kite is working to train staff at more than 30 additional centers, with an eventual target of 70 to 90 centers across the US. The latest information on authorized centers is available at https://www.yescarta.com/authorized-treatment-centers/.

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has approved axicabtagene ciloleucel (Yescarta™, formerly KTE-C19) for use in adults with relapsed or refractory large B-cell lymphoma who have received 2 or more lines of systemic therapy.

Axicabtagene ciloleucel is the first chimeric antigen receptor (CAR) T-cell therapy approved to treat lymphomas.

The approval encompasses diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and transformed follicular lymphoma.

Axicabtagene ciloleucel is not approved to treat primary central nervous system lymphoma.

The FDA’s approval of axicabtagene ciloleucel was based on results from the phase 2 ZUMA-1 trial. Updated results from this trial were presented at the AACR Annual Meeting 2017.

Risks

Axicabtagene ciloleucel has a Boxed Warning in its product label noting that the therapy can cause cytokine release syndrome (CRS) and neurologic toxicities. Full prescribing information for axicabtagene ciloleucel is available at https://www.yescarta.com/.

Because of the risk of CRS and neurologic toxicities, axicabtagene ciloleucel was approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use. The FDA is requiring that hospitals and clinics that dispense axicabtagene ciloleucel be specially certified.

As part of that certification, staff who prescribe, dispense, or administer axicabtagene ciloleucel are required to be trained to recognize and manage CRS and nervous system toxicities. In addition, patients must be informed of the potential serious side effects associated with axicabtagene ciloleucel and of the importance of promptly returning to the treatment site if side effects develop.

Additional information about the REMS program can be found at https://www.yescartarems.com/.

To further evaluate the long-term safety of axicabtagene ciloleucel, the FDA is requiring the manufacturer—Kite, a Gilead company—to conduct a post-marketing observational study of patients treated with axicabtagene ciloleucel.

Access and cost

The list price of axicabtagene ciloleucel is $373,000.

The product will be manufactured in Kite’s commercial manufacturing facility in El Segundo, California.

In 2017, Kite established a multi-disciplinary field team focused on providing education and logistics training for medical centers. Now, this team has provided final site certification to 16 centers, enabling them to make axicabtagene ciloleucel available to appropriate patients.

Kite is working to train staff at more than 30 additional centers, with an eventual target of 70 to 90 centers across the US. The latest information on authorized centers is available at https://www.yescarta.com/authorized-treatment-centers/.

mycosis fungoides

LONDON—Results of a phase 2 trial suggest the topical histone deacetylase (HDAC) inhibitor remetinostat can elicit responses in patients with early stage mycosis fungoides (MF).

At the highest dose level tested, remetinostat gel reduced the severity of skin lesions in 40% of patients and reduced the severity of pruritus in 80% of patients.

In addition, the HDAC inhibitor was considered well tolerated and did not produce systemic adverse effects.

These results were presented at the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force meeting, which took place October 13-15.

The study was sponsored by Medivir AB, which purchased remetinostat from TetraLogic Pharmaceuticals last year.

The trial of remetinostat enrolled 60 patients with stage IA-IIA MF across 5 clinical sites in the US. Patients were randomized to receive remetinostat gel 0.5% twice daily, remetinostat gel 1% once daily, or remetinostat gel 1% twice daily for up to 12 months.

The study’s primary endpoint was the proportion of patients with a confirmed response to therapy, assessed using the Composite Assessment of Index Lesion Severity.

The researchers observed a dose response, with patients in the 1% twice-daily arm having the highest proportion of confirmed responses.

Based on an intent-to-treat analysis, confirmed response rates were as follows:

The researchers also assessed the effect of remetinostat gel on the severity of pruritus. This was assessed monthly for the duration of the study using the visual analogue scale.

Among patients with clinically significant pruritus at baseline, those who received remetinostat gel 1% twice daily were most likely to have a clinically significant reduction in pruritus. This was defined as at least a 30 mm reduction in the visual analogue scale score sustained for more than 4 weeks.

The proportion of patients who had confirmed, clinically significant reductions in pruritus from baseline was 80% in the 1% twice-daily arm, 50% in the 0.5% twice-daily arm, and 37.5% in the 1% once-daily arm.

The researchers said remetinostat was generally well tolerated, with adverse events evenly distributed across the treatment arms. The most common adverse events were skin-related and mostly grade 1-2.

There were no signs of systemic adverse effects related to remetinostat, including those associated with systemic HDAC inhibitors.

Most patients remained on study for the maximum possible duration, and the median treatment time was 350 days.

Based on the outcomes of this study, Medivir expects to meet with regulatory authorities to discuss the design of a pivotal clinical program for remetinostat in MF.

mycosis fungoides

LONDON—Results of a phase 2 trial suggest the topical histone deacetylase (HDAC) inhibitor remetinostat can elicit responses in patients with early stage mycosis fungoides (MF).

At the highest dose level tested, remetinostat gel reduced the severity of skin lesions in 40% of patients and reduced the severity of pruritus in 80% of patients.

In addition, the HDAC inhibitor was considered well tolerated and did not produce systemic adverse effects.

These results were presented at the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force meeting, which took place October 13-15.

The study was sponsored by Medivir AB, which purchased remetinostat from TetraLogic Pharmaceuticals last year.

The trial of remetinostat enrolled 60 patients with stage IA-IIA MF across 5 clinical sites in the US. Patients were randomized to receive remetinostat gel 0.5% twice daily, remetinostat gel 1% once daily, or remetinostat gel 1% twice daily for up to 12 months.

The study’s primary endpoint was the proportion of patients with a confirmed response to therapy, assessed using the Composite Assessment of Index Lesion Severity.

The researchers observed a dose response, with patients in the 1% twice-daily arm having the highest proportion of confirmed responses.

Based on an intent-to-treat analysis, confirmed response rates were as follows:

The researchers also assessed the effect of remetinostat gel on the severity of pruritus. This was assessed monthly for the duration of the study using the visual analogue scale.

Among patients with clinically significant pruritus at baseline, those who received remetinostat gel 1% twice daily were most likely to have a clinically significant reduction in pruritus. This was defined as at least a 30 mm reduction in the visual analogue scale score sustained for more than 4 weeks.

The proportion of patients who had confirmed, clinically significant reductions in pruritus from baseline was 80% in the 1% twice-daily arm, 50% in the 0.5% twice-daily arm, and 37.5% in the 1% once-daily arm.

The researchers said remetinostat was generally well tolerated, with adverse events evenly distributed across the treatment arms. The most common adverse events were skin-related and mostly grade 1-2.

There were no signs of systemic adverse effects related to remetinostat, including those associated with systemic HDAC inhibitors.

Most patients remained on study for the maximum possible duration, and the median treatment time was 350 days.

Based on the outcomes of this study, Medivir expects to meet with regulatory authorities to discuss the design of a pivotal clinical program for remetinostat in MF.

mycosis fungoides

LONDON—Results of a phase 2 trial suggest the topical histone deacetylase (HDAC) inhibitor remetinostat can elicit responses in patients with early stage mycosis fungoides (MF).

At the highest dose level tested, remetinostat gel reduced the severity of skin lesions in 40% of patients and reduced the severity of pruritus in 80% of patients.

In addition, the HDAC inhibitor was considered well tolerated and did not produce systemic adverse effects.

These results were presented at the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force meeting, which took place October 13-15.

The study was sponsored by Medivir AB, which purchased remetinostat from TetraLogic Pharmaceuticals last year.

The trial of remetinostat enrolled 60 patients with stage IA-IIA MF across 5 clinical sites in the US. Patients were randomized to receive remetinostat gel 0.5% twice daily, remetinostat gel 1% once daily, or remetinostat gel 1% twice daily for up to 12 months.

The study’s primary endpoint was the proportion of patients with a confirmed response to therapy, assessed using the Composite Assessment of Index Lesion Severity.

The researchers observed a dose response, with patients in the 1% twice-daily arm having the highest proportion of confirmed responses.

Based on an intent-to-treat analysis, confirmed response rates were as follows:

The researchers also assessed the effect of remetinostat gel on the severity of pruritus. This was assessed monthly for the duration of the study using the visual analogue scale.

Among patients with clinically significant pruritus at baseline, those who received remetinostat gel 1% twice daily were most likely to have a clinically significant reduction in pruritus. This was defined as at least a 30 mm reduction in the visual analogue scale score sustained for more than 4 weeks.

The proportion of patients who had confirmed, clinically significant reductions in pruritus from baseline was 80% in the 1% twice-daily arm, 50% in the 0.5% twice-daily arm, and 37.5% in the 1% once-daily arm.

The researchers said remetinostat was generally well tolerated, with adverse events evenly distributed across the treatment arms. The most common adverse events were skin-related and mostly grade 1-2.

There were no signs of systemic adverse effects related to remetinostat, including those associated with systemic HDAC inhibitors.

Most patients remained on study for the maximum possible duration, and the median treatment time was 350 days.

Based on the outcomes of this study, Medivir expects to meet with regulatory authorities to discuss the design of a pivotal clinical program for remetinostat in MF.

Photo by Rhoda Baer

A new study suggests cryotherapy can reduce symptoms of chemotherapy-induced peripheral neuropathy (CIPN).

Researchers found that having chemotherapy patients wear frozen gloves and socks for 90-minute periods significantly reduced the incidence of CIPN symptoms.

Hiroshi Ishiguro, MD, PhD, of International University of Health and Welfare Hospital in Tochigi, Japan, and colleagues reported these findings in the Journal of the National Cancer Institute.

The researchers prospectively evaluated the efficacy of cryotherapy for preventing CIPN. Breast cancer patients treated weekly with paclitaxel (80 mg/m² for 1 hour) wore frozen gloves and socks on one side of their bodies for 90 minutes, including the entire duration of drug infusion.

The researchers then compared symptoms on the treated sides with those on the untreated sides.

The primary endpoint was CIPN incidence assessed by changes in tactile sensitivity from a pretreatment baseline. The researchers also assessed subjective symptoms, as reported in the Patient Neuropathy Questionnaire, and patients' manual dexterity.

Among the 40 patients studied, 4 did not reach the cumulative dose due to the occurrence of pneumonia, severe fatigue, liver dysfunction, and macular edema. Of the 36 remaining patients, none dropped out due to cold intolerance.

The incidence of objective and subjective signs of CIPN was clinically and statistically significantly lower on the intervention side than on the control side for most measurements, which includes (among other measures):

• Hand tactile sensitivity—27.8% and 80.6%, respectively (odds ratio[OR]= 20.00, P<0.001)
• Foot tactile sensitivity—25.0% and 63.9%, respectively (OR=infinite, P<0.001)
• Hand warm sense—8.8% and 32.4%, respectively (OR=9.00, P=0.02)
• Foot warm sense—33.4% and 57.6%, respectively (OR=5.00, P=0.04)
• Hand cold sense—2.8% and 13.9%, respectively (OR=infinite, P=0.13)
• Foot cold sense—12.6% and 18.8%, respectively (OR=2.00, P=0.69)
• Severe CIPN in the hand according to the Patient Neuropathy Questionnaire—2.8% and 41.7%, respectively (OR=infinite, P<0.001)
• Severe CIPN in the foot according to the Patient Neuropathy Questionnaire—2.8% and 36.1%, respectively (OR=infinite, P<0.001).
  

Photo by Rhoda Baer

A new study suggests cryotherapy can reduce symptoms of chemotherapy-induced peripheral neuropathy (CIPN).

Researchers found that having chemotherapy patients wear frozen gloves and socks for 90-minute periods significantly reduced the incidence of CIPN symptoms.

Hiroshi Ishiguro, MD, PhD, of International University of Health and Welfare Hospital in Tochigi, Japan, and colleagues reported these findings in the Journal of the National Cancer Institute.

The researchers prospectively evaluated the efficacy of cryotherapy for preventing CIPN. Breast cancer patients treated weekly with paclitaxel (80 mg/m² for 1 hour) wore frozen gloves and socks on one side of their bodies for 90 minutes, including the entire duration of drug infusion.

The researchers then compared symptoms on the treated sides with those on the untreated sides.

The primary endpoint was CIPN incidence assessed by changes in tactile sensitivity from a pretreatment baseline. The researchers also assessed subjective symptoms, as reported in the Patient Neuropathy Questionnaire, and patients' manual dexterity.

Among the 40 patients studied, 4 did not reach the cumulative dose due to the occurrence of pneumonia, severe fatigue, liver dysfunction, and macular edema. Of the 36 remaining patients, none dropped out due to cold intolerance.

The incidence of objective and subjective signs of CIPN was clinically and statistically significantly lower on the intervention side than on the control side for most measurements, which includes (among other measures):

• Hand tactile sensitivity—27.8% and 80.6%, respectively (odds ratio[OR]= 20.00, P<0.001)
• Foot tactile sensitivity—25.0% and 63.9%, respectively (OR=infinite, P<0.001)
• Hand warm sense—8.8% and 32.4%, respectively (OR=9.00, P=0.02)
• Foot warm sense—33.4% and 57.6%, respectively (OR=5.00, P=0.04)
• Hand cold sense—2.8% and 13.9%, respectively (OR=infinite, P=0.13)
• Foot cold sense—12.6% and 18.8%, respectively (OR=2.00, P=0.69)
• Severe CIPN in the hand according to the Patient Neuropathy Questionnaire—2.8% and 41.7%, respectively (OR=infinite, P<0.001)
• Severe CIPN in the foot according to the Patient Neuropathy Questionnaire—2.8% and 36.1%, respectively (OR=infinite, P<0.001).
  

Photo by Rhoda Baer

A new study suggests cryotherapy can reduce symptoms of chemotherapy-induced peripheral neuropathy (CIPN).

Researchers found that having chemotherapy patients wear frozen gloves and socks for 90-minute periods significantly reduced the incidence of CIPN symptoms.

Hiroshi Ishiguro, MD, PhD, of International University of Health and Welfare Hospital in Tochigi, Japan, and colleagues reported these findings in the Journal of the National Cancer Institute.

The researchers prospectively evaluated the efficacy of cryotherapy for preventing CIPN. Breast cancer patients treated weekly with paclitaxel (80 mg/m² for 1 hour) wore frozen gloves and socks on one side of their bodies for 90 minutes, including the entire duration of drug infusion.

The researchers then compared symptoms on the treated sides with those on the untreated sides.

The primary endpoint was CIPN incidence assessed by changes in tactile sensitivity from a pretreatment baseline. The researchers also assessed subjective symptoms, as reported in the Patient Neuropathy Questionnaire, and patients' manual dexterity.

Among the 40 patients studied, 4 did not reach the cumulative dose due to the occurrence of pneumonia, severe fatigue, liver dysfunction, and macular edema. Of the 36 remaining patients, none dropped out due to cold intolerance.

The incidence of objective and subjective signs of CIPN was clinically and statistically significantly lower on the intervention side than on the control side for most measurements, which includes (among other measures):

• Hand tactile sensitivity—27.8% and 80.6%, respectively (odds ratio[OR]= 20.00, P<0.001)
• Foot tactile sensitivity—25.0% and 63.9%, respectively (OR=infinite, P<0.001)
• Hand warm sense—8.8% and 32.4%, respectively (OR=9.00, P=0.02)
• Foot warm sense—33.4% and 57.6%, respectively (OR=5.00, P=0.04)
• Hand cold sense—2.8% and 13.9%, respectively (OR=infinite, P=0.13)
• Foot cold sense—12.6% and 18.8%, respectively (OR=2.00, P=0.69)
• Severe CIPN in the hand according to the Patient Neuropathy Questionnaire—2.8% and 41.7%, respectively (OR=infinite, P<0.001)
• Severe CIPN in the foot according to the Patient Neuropathy Questionnaire—2.8% and 36.1%, respectively (OR=infinite, P<0.001).
  

Photo by Rhoda Baer

Countries with the lowest opportunities for natural selection have higher cancer rates than countries with the highest opportunities for natural selection, according to a study published in Evolutionary Applications.

Researchers said this is because modern medicine is enabling people to survive cancers, and their genetic backgrounds are passing from one generation to the next.

The team said the rate of some cancers has doubled and even quadrupled over the past 100 to 150 years, and human evolution has moved away from “survival of the fittest.”

“Modern medicine has enabled the human species to live much longer than would otherwise be expected in the natural world,” said study author Maciej Henneberg, PhD, DSc, of the University of Adelaide in South Australia.

“Besides the obvious benefits that modern medicine gives, it also brings with it an unexpected side-effect—allowing genetic material to be passed from one generation to the next that predisposes people to have poor health, such as type 1 diabetes or cancer.”

“Because of the quality of our healthcare in western society, we have almost removed natural selection as the ‘janitor of the gene pool.’ Unfortunately, the accumulation of genetic mutations over time and across multiple generations is like a delayed death sentence.”

Country comparison

The researchers studied global cancer data from the World Health Organization as well as other health and socioeconomic data from the United Nations and the World Bank of 173 countries. The team compared the top 10 countries with the highest opportunities for natural selection to the 10 countries with the lowest opportunities for natural selection.

“We looked at countries that offered the greatest opportunity to survive cancer compared with those that didn’t,” said study author Wenpeng You, a PhD student at the University of Adelaide. “This does not only take into account factors such as socioeconomic status, urbanization, and quality of medical services but also low mortality and fertility rates, which are the 2 distinguishing features in the ‘better’ world.”

“Countries with low mortality rates may allow more people with cancer genetic background to reproduce and pass cancer genes/mutations to the next generation. Meanwhile, low fertility rates in these countries may not be able to have diverse biological variations to provide the opportunity for selecting a naturally fit population—for example, people without or with less cancer genetic background. Low mortality rate and low fertility rate in the ‘better’ world may have formed a self-reinforcing cycle which has accumulated cancer genetic background at a greater rate than previously thought.”

Based on the researchers’ analysis, the 20 countries are:

Cancer incidence

The researchers found the rates of most cancers were higher in the 10 countries with the lowest opportunities for natural selection. The incidence of all cancers was 2.326 times higher in the low-opportunity countries than the high-opportunity ones.

The increased incidences of hematologic malignancies were as follows:

• Non-Hodgkin lymphoma—2.019 times higher in the low-opportunity countries
• Hodgkin lymphoma—3.314 times higher in the low-opportunity countries
• Leukemia—3.574 times higher in the low-opportunity countries
• Multiple myeloma—4.257 times higher in the low-opportunity countries .

Dr Henneberg said that, having removed natural selection as the “janitor of the gene pool,” our modern society is faced with a controversial issue.

“It may be that the only way humankind can be rid of cancer once and for all is through genetic engineering—to repair our genes and take cancer out of the equation,” he said.

Photo by Rhoda Baer

Countries with the lowest opportunities for natural selection have higher cancer rates than countries with the highest opportunities for natural selection, according to a study published in Evolutionary Applications.

Researchers said this is because modern medicine is enabling people to survive cancers, and their genetic backgrounds are passing from one generation to the next.

The team said the rate of some cancers has doubled and even quadrupled over the past 100 to 150 years, and human evolution has moved away from “survival of the fittest.”

“Modern medicine has enabled the human species to live much longer than would otherwise be expected in the natural world,” said study author Maciej Henneberg, PhD, DSc, of the University of Adelaide in South Australia.

“Besides the obvious benefits that modern medicine gives, it also brings with it an unexpected side-effect—allowing genetic material to be passed from one generation to the next that predisposes people to have poor health, such as type 1 diabetes or cancer.”

“Because of the quality of our healthcare in western society, we have almost removed natural selection as the ‘janitor of the gene pool.’ Unfortunately, the accumulation of genetic mutations over time and across multiple generations is like a delayed death sentence.”

Country comparison

The researchers studied global cancer data from the World Health Organization as well as other health and socioeconomic data from the United Nations and the World Bank of 173 countries. The team compared the top 10 countries with the highest opportunities for natural selection to the 10 countries with the lowest opportunities for natural selection.

“We looked at countries that offered the greatest opportunity to survive cancer compared with those that didn’t,” said study author Wenpeng You, a PhD student at the University of Adelaide. “This does not only take into account factors such as socioeconomic status, urbanization, and quality of medical services but also low mortality and fertility rates, which are the 2 distinguishing features in the ‘better’ world.”

“Countries with low mortality rates may allow more people with cancer genetic background to reproduce and pass cancer genes/mutations to the next generation. Meanwhile, low fertility rates in these countries may not be able to have diverse biological variations to provide the opportunity for selecting a naturally fit population—for example, people without or with less cancer genetic background. Low mortality rate and low fertility rate in the ‘better’ world may have formed a self-reinforcing cycle which has accumulated cancer genetic background at a greater rate than previously thought.”

Based on the researchers’ analysis, the 20 countries are:

Cancer incidence

The researchers found the rates of most cancers were higher in the 10 countries with the lowest opportunities for natural selection. The incidence of all cancers was 2.326 times higher in the low-opportunity countries than the high-opportunity ones.

The increased incidences of hematologic malignancies were as follows:

• Non-Hodgkin lymphoma—2.019 times higher in the low-opportunity countries
• Hodgkin lymphoma—3.314 times higher in the low-opportunity countries
• Leukemia—3.574 times higher in the low-opportunity countries
• Multiple myeloma—4.257 times higher in the low-opportunity countries .

Dr Henneberg said that, having removed natural selection as the “janitor of the gene pool,” our modern society is faced with a controversial issue.

“It may be that the only way humankind can be rid of cancer once and for all is through genetic engineering—to repair our genes and take cancer out of the equation,” he said.

Photo by Rhoda Baer

Countries with the lowest opportunities for natural selection have higher cancer rates than countries with the highest opportunities for natural selection, according to a study published in Evolutionary Applications.

Researchers said this is because modern medicine is enabling people to survive cancers, and their genetic backgrounds are passing from one generation to the next.

The team said the rate of some cancers has doubled and even quadrupled over the past 100 to 150 years, and human evolution has moved away from “survival of the fittest.”

“Modern medicine has enabled the human species to live much longer than would otherwise be expected in the natural world,” said study author Maciej Henneberg, PhD, DSc, of the University of Adelaide in South Australia.

“Besides the obvious benefits that modern medicine gives, it also brings with it an unexpected side-effect—allowing genetic material to be passed from one generation to the next that predisposes people to have poor health, such as type 1 diabetes or cancer.”

“Because of the quality of our healthcare in western society, we have almost removed natural selection as the ‘janitor of the gene pool.’ Unfortunately, the accumulation of genetic mutations over time and across multiple generations is like a delayed death sentence.”

Country comparison

The researchers studied global cancer data from the World Health Organization as well as other health and socioeconomic data from the United Nations and the World Bank of 173 countries. The team compared the top 10 countries with the highest opportunities for natural selection to the 10 countries with the lowest opportunities for natural selection.

“We looked at countries that offered the greatest opportunity to survive cancer compared with those that didn’t,” said study author Wenpeng You, a PhD student at the University of Adelaide. “This does not only take into account factors such as socioeconomic status, urbanization, and quality of medical services but also low mortality and fertility rates, which are the 2 distinguishing features in the ‘better’ world.”

“Countries with low mortality rates may allow more people with cancer genetic background to reproduce and pass cancer genes/mutations to the next generation. Meanwhile, low fertility rates in these countries may not be able to have diverse biological variations to provide the opportunity for selecting a naturally fit population—for example, people without or with less cancer genetic background. Low mortality rate and low fertility rate in the ‘better’ world may have formed a self-reinforcing cycle which has accumulated cancer genetic background at a greater rate than previously thought.”

Based on the researchers’ analysis, the 20 countries are:

Cancer incidence

The researchers found the rates of most cancers were higher in the 10 countries with the lowest opportunities for natural selection. The incidence of all cancers was 2.326 times higher in the low-opportunity countries than the high-opportunity ones.

The increased incidences of hematologic malignancies were as follows:

• Non-Hodgkin lymphoma—2.019 times higher in the low-opportunity countries
• Hodgkin lymphoma—3.314 times higher in the low-opportunity countries
• Leukemia—3.574 times higher in the low-opportunity countries
• Multiple myeloma—4.257 times higher in the low-opportunity countries .

Dr Henneberg said that, having removed natural selection as the “janitor of the gene pool,” our modern society is faced with a controversial issue.

“It may be that the only way humankind can be rid of cancer once and for all is through genetic engineering—to repair our genes and take cancer out of the equation,” he said.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has announced the release of the newly completed NCCN Radiation Therapy Compendium™.

This resource includes information designed to support clinical decision-making regarding the use of radiation therapy in cancer patients.

The content is based on the NCCN Clinical Practice Guidelines in Oncology and includes information from the 41 guidelines that reference radiation therapy.

“By compiling every recommendation for radiation therapy in one place, we’ve made it significantly easier for specialists . . .  to stay up-to-date on the very latest recommendations, regardless of how many different cancer types they treat,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“This targeted content provides radiation oncologists with the specific, cutting-edge information they need, without forcing them to sift through any extraneous information. It’s part of our ongoing effort to always provide the most pertinent data on emerging treatment practices in the clearest, most efficient way possible.”

The NCCN Radiation Therapy Compendium includes a full complement of radiation therapy recommendations found in the current NCCN guidelines, including specific treatment modalities such as 2D/3D conformal external beam radiation therapy, intensity modulated radiation therapy, intra-operative radiation therapy, stereotactic radiosurgery/stereotactic body radiotherapy/stereotactic ablative body radiotherapy, image-guided radiation therapy, low dose-rate/high dose-rate brachytherapy, radioisotope, and particle therapy.

NCCN first announced the launch of the Radiation Therapy Compendium in March at the NCCN Annual Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care.

At the time, the NCCN released a preliminary version of the compendium featuring 24 cancer types. The newly completed version now contains all 41 disease sites that are currently being treated using radiation therapy.

The compendium will be updated on a continual basis in conjunction with the library of clinical guidelines.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium. The compendium is available free-of-charge through March 2018.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has announced the release of the newly completed NCCN Radiation Therapy Compendium™.

This resource includes information designed to support clinical decision-making regarding the use of radiation therapy in cancer patients.

The content is based on the NCCN Clinical Practice Guidelines in Oncology and includes information from the 41 guidelines that reference radiation therapy.

“By compiling every recommendation for radiation therapy in one place, we’ve made it significantly easier for specialists . . .  to stay up-to-date on the very latest recommendations, regardless of how many different cancer types they treat,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“This targeted content provides radiation oncologists with the specific, cutting-edge information they need, without forcing them to sift through any extraneous information. It’s part of our ongoing effort to always provide the most pertinent data on emerging treatment practices in the clearest, most efficient way possible.”

The NCCN Radiation Therapy Compendium includes a full complement of radiation therapy recommendations found in the current NCCN guidelines, including specific treatment modalities such as 2D/3D conformal external beam radiation therapy, intensity modulated radiation therapy, intra-operative radiation therapy, stereotactic radiosurgery/stereotactic body radiotherapy/stereotactic ablative body radiotherapy, image-guided radiation therapy, low dose-rate/high dose-rate brachytherapy, radioisotope, and particle therapy.

NCCN first announced the launch of the Radiation Therapy Compendium in March at the NCCN Annual Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care.

At the time, the NCCN released a preliminary version of the compendium featuring 24 cancer types. The newly completed version now contains all 41 disease sites that are currently being treated using radiation therapy.

The compendium will be updated on a continual basis in conjunction with the library of clinical guidelines.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium. The compendium is available free-of-charge through March 2018.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has announced the release of the newly completed NCCN Radiation Therapy Compendium™.

This resource includes information designed to support clinical decision-making regarding the use of radiation therapy in cancer patients.

The content is based on the NCCN Clinical Practice Guidelines in Oncology and includes information from the 41 guidelines that reference radiation therapy.

“By compiling every recommendation for radiation therapy in one place, we’ve made it significantly easier for specialists . . .  to stay up-to-date on the very latest recommendations, regardless of how many different cancer types they treat,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“This targeted content provides radiation oncologists with the specific, cutting-edge information they need, without forcing them to sift through any extraneous information. It’s part of our ongoing effort to always provide the most pertinent data on emerging treatment practices in the clearest, most efficient way possible.”

The NCCN Radiation Therapy Compendium includes a full complement of radiation therapy recommendations found in the current NCCN guidelines, including specific treatment modalities such as 2D/3D conformal external beam radiation therapy, intensity modulated radiation therapy, intra-operative radiation therapy, stereotactic radiosurgery/stereotactic body radiotherapy/stereotactic ablative body radiotherapy, image-guided radiation therapy, low dose-rate/high dose-rate brachytherapy, radioisotope, and particle therapy.

NCCN first announced the launch of the Radiation Therapy Compendium in March at the NCCN Annual Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care.

At the time, the NCCN released a preliminary version of the compendium featuring 24 cancer types. The newly completed version now contains all 41 disease sites that are currently being treated using radiation therapy.

The compendium will be updated on a continual basis in conjunction with the library of clinical guidelines.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium. The compendium is available free-of-charge through March 2018.