Lymphoma & Plasma Cell Disorders

Using FDG-PET (fluorodeoxyglucose positron emission tomography) imaging to gauge treatment response after the first two rounds of ABVD therapy helps to determine which patients with advanced Hodgkin’s lymphoma should be switched to a more aggressive eBEACOPP regimen, according to the results of the Southwest Oncology Group (SWOG) S0816 study.

In this large U.S. trial of PET scanning to guide treatment approach in people with high-risk stage II or stage III-IV Hodgkin’s lymphoma, progression-free survival at 2 years for those with early interim positive PET scans was 64%, which is much higher than the expected progression-free survival of 15%-30%, according to Dr. Oliver Press, a SWOG member at Fred Hutchinson Cancer Research Center and the lead author of study, which was published ahead of print in the Journal of Clinical Oncology (2016 April 11. doi: 10.1200/JCO.2015.63.1119).

Fred Hutchinson

In addition, just 20% of patients in the trial were exposed to eBEACOPP, which usually results in infertility, can cause sustained heart or lung damage, and increases the risk of secondary cancers.

Researchers recruited 358 Hodgkin’s patients to the trial and were able to evaluate 331 of them. All trial volunteers were given two rounds of standard ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, followed by a PET scan. If the scan was negative, patients received four more cycles of ABVD. If the scan was positive, with a Deauville score of 4-5, they were advised to switch to eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), a seven-drug combination used in Europe. Of 60 patients with positive interim PET scans, 11 patients declined to switch, and 49 switched as planned to six cycles of eBEACOPP.

With a median follow-up of nearly 40 months, the Kaplan-Meier estimate for 2-year overall survival was 98%, and the 2-year estimate for progression-free survival was 79%. In the subset of patients who had positive PET scans after two cycles of ABVD, the 2-year estimate for progression-free survival was 64%, more than double the expected remission rate.

At least seven phase II and III cooperative group studies are underway testing this approach in advanced-stage Hodgkin’s lymphoma, the researchers wrote. “We hope that in the future, molecular biomarker studies at initial diagnosis, or the combination of biomarkers and molecular imaging, may define patients who require more intense therapy with eBEACOPP or other novel targeted drugs with greater accuracy than is achievable with current technology.”

The study was funded by the National Cancer Institute, the David and Patricia Giuliani Family Foundation, the Lymphoma Foundation, the Adam Spector Fund for Hodgkin Research, and the Ernest & Jeanette Dicker Charitable Foundation.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Using FDG-PET (fluorodeoxyglucose positron emission tomography) imaging to gauge treatment response after the first two rounds of ABVD therapy helps to determine which patients with advanced Hodgkin’s lymphoma should be switched to a more aggressive eBEACOPP regimen, according to the results of the Southwest Oncology Group (SWOG) S0816 study.

In this large U.S. trial of PET scanning to guide treatment approach in people with high-risk stage II or stage III-IV Hodgkin’s lymphoma, progression-free survival at 2 years for those with early interim positive PET scans was 64%, which is much higher than the expected progression-free survival of 15%-30%, according to Dr. Oliver Press, a SWOG member at Fred Hutchinson Cancer Research Center and the lead author of study, which was published ahead of print in the Journal of Clinical Oncology (2016 April 11. doi: 10.1200/JCO.2015.63.1119).

Fred Hutchinson

In addition, just 20% of patients in the trial were exposed to eBEACOPP, which usually results in infertility, can cause sustained heart or lung damage, and increases the risk of secondary cancers.

Researchers recruited 358 Hodgkin’s patients to the trial and were able to evaluate 331 of them. All trial volunteers were given two rounds of standard ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, followed by a PET scan. If the scan was negative, patients received four more cycles of ABVD. If the scan was positive, with a Deauville score of 4-5, they were advised to switch to eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), a seven-drug combination used in Europe. Of 60 patients with positive interim PET scans, 11 patients declined to switch, and 49 switched as planned to six cycles of eBEACOPP.

With a median follow-up of nearly 40 months, the Kaplan-Meier estimate for 2-year overall survival was 98%, and the 2-year estimate for progression-free survival was 79%. In the subset of patients who had positive PET scans after two cycles of ABVD, the 2-year estimate for progression-free survival was 64%, more than double the expected remission rate.

At least seven phase II and III cooperative group studies are underway testing this approach in advanced-stage Hodgkin’s lymphoma, the researchers wrote. “We hope that in the future, molecular biomarker studies at initial diagnosis, or the combination of biomarkers and molecular imaging, may define patients who require more intense therapy with eBEACOPP or other novel targeted drugs with greater accuracy than is achievable with current technology.”

The study was funded by the National Cancer Institute, the David and Patricia Giuliani Family Foundation, the Lymphoma Foundation, the Adam Spector Fund for Hodgkin Research, and the Ernest & Jeanette Dicker Charitable Foundation.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Using FDG-PET (fluorodeoxyglucose positron emission tomography) imaging to gauge treatment response after the first two rounds of ABVD therapy helps to determine which patients with advanced Hodgkin’s lymphoma should be switched to a more aggressive eBEACOPP regimen, according to the results of the Southwest Oncology Group (SWOG) S0816 study.

In this large U.S. trial of PET scanning to guide treatment approach in people with high-risk stage II or stage III-IV Hodgkin’s lymphoma, progression-free survival at 2 years for those with early interim positive PET scans was 64%, which is much higher than the expected progression-free survival of 15%-30%, according to Dr. Oliver Press, a SWOG member at Fred Hutchinson Cancer Research Center and the lead author of study, which was published ahead of print in the Journal of Clinical Oncology (2016 April 11. doi: 10.1200/JCO.2015.63.1119).

Fred Hutchinson

In addition, just 20% of patients in the trial were exposed to eBEACOPP, which usually results in infertility, can cause sustained heart or lung damage, and increases the risk of secondary cancers.

Researchers recruited 358 Hodgkin’s patients to the trial and were able to evaluate 331 of them. All trial volunteers were given two rounds of standard ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, followed by a PET scan. If the scan was negative, patients received four more cycles of ABVD. If the scan was positive, with a Deauville score of 4-5, they were advised to switch to eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), a seven-drug combination used in Europe. Of 60 patients with positive interim PET scans, 11 patients declined to switch, and 49 switched as planned to six cycles of eBEACOPP.

With a median follow-up of nearly 40 months, the Kaplan-Meier estimate for 2-year overall survival was 98%, and the 2-year estimate for progression-free survival was 79%. In the subset of patients who had positive PET scans after two cycles of ABVD, the 2-year estimate for progression-free survival was 64%, more than double the expected remission rate.

At least seven phase II and III cooperative group studies are underway testing this approach in advanced-stage Hodgkin’s lymphoma, the researchers wrote. “We hope that in the future, molecular biomarker studies at initial diagnosis, or the combination of biomarkers and molecular imaging, may define patients who require more intense therapy with eBEACOPP or other novel targeted drugs with greater accuracy than is achievable with current technology.”

The study was funded by the National Cancer Institute, the David and Patricia Giuliani Family Foundation, the Lymphoma Foundation, the Adam Spector Fund for Hodgkin Research, and the Ernest & Jeanette Dicker Charitable Foundation.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Another oral, small-molecule therapy called CUDC-907 is emerging from phase I testing as a treatment option for patients with relapsed or refractory lymphoma and multiple myeloma.

The CUDC-907 dose to be used in phase II studies will be 60 mg on a 5-days-on/2-days-off dosing schedule, according to Dr. Anas Younes of Memorial Sloan Kettering Cancer Center, New York, and his colleagues. A dose-expansion trial of this dose is ongoing, and the drug appears to be useful in particular for patients with refractory and relapsed diffuse large B-cell lymphoma.

WikimediaCommons/Copyright © 2011 Michael Bonert.

The researchers tested CUDC-907, which is designed to inhibit histone deacetylase and PI3K enzyme pathways, for overall safety and response in 44 patients at four cancer centers. All participants had lymphoma or multiple myeloma and were refractory to treatment or had relapsed after two or more previous regimens.

The 44 participants were sequentially assigned to 21-day cycles of CUDC-907: 10 to once daily, 12 to twice weekly, 15 to three times weekly, and 7 to daily for 5 days followed by a 2-day break. The maximum tolerated doses were 60 mg for the once-daily schedule, 150 mg for the twice-weekly schedule, 150 mg for the three-times-weekly schedule, and 60 mg for the 5-on/2-off schedule. At data cutoff, 37 of the 44 patients had discontinued CUDC-907 because of disease progression, Dr. Younes and his associates reported in a study published online (Lancet Oncol. 2016 Mar 31. doi: 10.1016/S1470-2045(15)00584-7).

Four dose-limiting toxicities occurred in 3 of 40 evaluable patients. Grade 3 or worse adverse events occurred in 19 of 44 patients: 9 had thrombocytopenia, 3 had neutropenia, 3 had hyperglycemia. Adverse events led to dose reductions in six patients and treatment discontinuation in seven.

Of 37 response-evaluable patients, two had complete responses and three had partial responses. All five were seen in the subgroup of nine patients with diffuse large B-cell lymphoma, and three occurred in the five patients with transformed follicular disease. The 21 patients with stable disease included those with diffuse large B-cell lymphoma, Hodgkin’s lymphoma, and multiple myeloma. This ongoing trial is registered at ClinicalTrials.gov as NCT01742988.

The study was sponsored by Curis, the maker of CUDC-907, and the Leukemia and Lymphoma Society. Five of the 15 investigators are employees of Curis.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Another oral, small-molecule therapy called CUDC-907 is emerging from phase I testing as a treatment option for patients with relapsed or refractory lymphoma and multiple myeloma.

The CUDC-907 dose to be used in phase II studies will be 60 mg on a 5-days-on/2-days-off dosing schedule, according to Dr. Anas Younes of Memorial Sloan Kettering Cancer Center, New York, and his colleagues. A dose-expansion trial of this dose is ongoing, and the drug appears to be useful in particular for patients with refractory and relapsed diffuse large B-cell lymphoma.

WikimediaCommons/Copyright © 2011 Michael Bonert.

The researchers tested CUDC-907, which is designed to inhibit histone deacetylase and PI3K enzyme pathways, for overall safety and response in 44 patients at four cancer centers. All participants had lymphoma or multiple myeloma and were refractory to treatment or had relapsed after two or more previous regimens.

The 44 participants were sequentially assigned to 21-day cycles of CUDC-907: 10 to once daily, 12 to twice weekly, 15 to three times weekly, and 7 to daily for 5 days followed by a 2-day break. The maximum tolerated doses were 60 mg for the once-daily schedule, 150 mg for the twice-weekly schedule, 150 mg for the three-times-weekly schedule, and 60 mg for the 5-on/2-off schedule. At data cutoff, 37 of the 44 patients had discontinued CUDC-907 because of disease progression, Dr. Younes and his associates reported in a study published online (Lancet Oncol. 2016 Mar 31. doi: 10.1016/S1470-2045(15)00584-7).

Four dose-limiting toxicities occurred in 3 of 40 evaluable patients. Grade 3 or worse adverse events occurred in 19 of 44 patients: 9 had thrombocytopenia, 3 had neutropenia, 3 had hyperglycemia. Adverse events led to dose reductions in six patients and treatment discontinuation in seven.

Of 37 response-evaluable patients, two had complete responses and three had partial responses. All five were seen in the subgroup of nine patients with diffuse large B-cell lymphoma, and three occurred in the five patients with transformed follicular disease. The 21 patients with stable disease included those with diffuse large B-cell lymphoma, Hodgkin’s lymphoma, and multiple myeloma. This ongoing trial is registered at ClinicalTrials.gov as NCT01742988.

The study was sponsored by Curis, the maker of CUDC-907, and the Leukemia and Lymphoma Society. Five of the 15 investigators are employees of Curis.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Another oral, small-molecule therapy called CUDC-907 is emerging from phase I testing as a treatment option for patients with relapsed or refractory lymphoma and multiple myeloma.

The CUDC-907 dose to be used in phase II studies will be 60 mg on a 5-days-on/2-days-off dosing schedule, according to Dr. Anas Younes of Memorial Sloan Kettering Cancer Center, New York, and his colleagues. A dose-expansion trial of this dose is ongoing, and the drug appears to be useful in particular for patients with refractory and relapsed diffuse large B-cell lymphoma.

WikimediaCommons/Copyright © 2011 Michael Bonert.

The researchers tested CUDC-907, which is designed to inhibit histone deacetylase and PI3K enzyme pathways, for overall safety and response in 44 patients at four cancer centers. All participants had lymphoma or multiple myeloma and were refractory to treatment or had relapsed after two or more previous regimens.

The 44 participants were sequentially assigned to 21-day cycles of CUDC-907: 10 to once daily, 12 to twice weekly, 15 to three times weekly, and 7 to daily for 5 days followed by a 2-day break. The maximum tolerated doses were 60 mg for the once-daily schedule, 150 mg for the twice-weekly schedule, 150 mg for the three-times-weekly schedule, and 60 mg for the 5-on/2-off schedule. At data cutoff, 37 of the 44 patients had discontinued CUDC-907 because of disease progression, Dr. Younes and his associates reported in a study published online (Lancet Oncol. 2016 Mar 31. doi: 10.1016/S1470-2045(15)00584-7).

Four dose-limiting toxicities occurred in 3 of 40 evaluable patients. Grade 3 or worse adverse events occurred in 19 of 44 patients: 9 had thrombocytopenia, 3 had neutropenia, 3 had hyperglycemia. Adverse events led to dose reductions in six patients and treatment discontinuation in seven.

Of 37 response-evaluable patients, two had complete responses and three had partial responses. All five were seen in the subgroup of nine patients with diffuse large B-cell lymphoma, and three occurred in the five patients with transformed follicular disease. The 21 patients with stable disease included those with diffuse large B-cell lymphoma, Hodgkin’s lymphoma, and multiple myeloma. This ongoing trial is registered at ClinicalTrials.gov as NCT01742988.

The study was sponsored by Curis, the maker of CUDC-907, and the Leukemia and Lymphoma Society. Five of the 15 investigators are employees of Curis.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Prescription medications

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has granted accelerated approval for venetoclax (Venclexta) to treat patients with chronic lymphocytic leukemia (CLL) who have 17p deletion and have received at least one prior therapy.

Venetoclax will be available in the US within about a week, according to the companies developing the drug, AbbVie and Genentech (a member of the

Roche Group).

The companies said they plan to offer patient assistance programs for qualifying patients who wish to receive venetoclax.

Venetoclax (formerly ABT-199) is the first FDA-approved treatment that targets the BCL-2 protein, which is overexpressed in many patients with CLL.

The drug is indicated for daily use after 17p deletion is confirmed via the FDA-approved companion diagnostic Vysis CLL FISH probe kit, which is manufactured by Abbott Molecular.

The FDA granted venetoclax accelerated approval rather than traditional approval because the drug has not yet shown a clinical benefit. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of venetoclax for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted venetoclax breakthrough therapy designation, priority review status, and orphan drug designation.

Phase 2 trial

Results from the pivotal phase 2 trial of venetoclax (M13-982, NCT01889186) were presented at the 2015 ASH Annual Meeting. According to those data, the trial enrolled 107 patients with relapsed or refractory CLL and 17p deletion.

Patients received venetoclax at 400 mg once daily following a weekly ramp-up schedule for the first 5 weeks. The primary endpoint was overall response rate, as determined by an independent review committee.

Eighty-five patients responded to treatment, for an overall response rate of 79.4%. Eight patients (7.5%) achieved a complete response or complete response with incomplete count recovery, 3 (2.8%) had a near partial response, and 74 (69.2%) had a partial response. Twenty-two patients (20.6%) did not respond.

As of the ASH presentation, the median duration of response had not been reached. The same was true for progression-free survival and overall survival. The progression-free survival estimate for 12 months was 72.0%, and the overall survival estimate was 86.7%.

Treatment-emergent adverse events of any grade occurred in 96% of patients. The most frequent were neutropenia (43%), diarrhea (29%), nausea (29%), anemia (27%), fatigue (22%), pyrexia (20%), thrombocytopenia (19%), hyperphosphatemia (16%), vomiting (15%), and upper respiratory tract infection (15%). (About 22% of patients had neutropenia at baseline.)

The most frequent grade 3/4 adverse events were neutropenia (40%), anemia (18%), and thrombocytopenia (15%). Infections occurred in 72% of patients, with 20% of patients experiencing grade 3 or higher infections.

Serious adverse events occurred in 55% of patients, the most common being pyrexia (7%), autoimmune hemolytic anemia (7%), pneumonia (6%), and febrile neutropenia (5%).

Laboratory tumor lysis syndrome (TLS) occurred in 5 patients during the ramp-up period only. Two patients required a dose interruption of 1 day each. There were no clinical TLS events.

In the past, TLS has caused deaths in patients receiving venetoclax. In response, AbbVie stopped dose-escalation in patients receiving the drug and suspended enrollment in phase 1 trials.

However, researchers subsequently found that a modified dosing schedule, prophylaxis, and patient monitoring can reduce the risk of TLS.

Venetoclax is currently being evaluated in phase 3 trials for the treatment of relapsed, refractory, and previously untreated CLL.

Prescription medications

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has granted accelerated approval for venetoclax (Venclexta) to treat patients with chronic lymphocytic leukemia (CLL) who have 17p deletion and have received at least one prior therapy.

Venetoclax will be available in the US within about a week, according to the companies developing the drug, AbbVie and Genentech (a member of the

Roche Group).

The companies said they plan to offer patient assistance programs for qualifying patients who wish to receive venetoclax.

Venetoclax (formerly ABT-199) is the first FDA-approved treatment that targets the BCL-2 protein, which is overexpressed in many patients with CLL.

The drug is indicated for daily use after 17p deletion is confirmed via the FDA-approved companion diagnostic Vysis CLL FISH probe kit, which is manufactured by Abbott Molecular.

The FDA granted venetoclax accelerated approval rather than traditional approval because the drug has not yet shown a clinical benefit. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of venetoclax for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted venetoclax breakthrough therapy designation, priority review status, and orphan drug designation.

Phase 2 trial

Results from the pivotal phase 2 trial of venetoclax (M13-982, NCT01889186) were presented at the 2015 ASH Annual Meeting. According to those data, the trial enrolled 107 patients with relapsed or refractory CLL and 17p deletion.

Patients received venetoclax at 400 mg once daily following a weekly ramp-up schedule for the first 5 weeks. The primary endpoint was overall response rate, as determined by an independent review committee.

Eighty-five patients responded to treatment, for an overall response rate of 79.4%. Eight patients (7.5%) achieved a complete response or complete response with incomplete count recovery, 3 (2.8%) had a near partial response, and 74 (69.2%) had a partial response. Twenty-two patients (20.6%) did not respond.

As of the ASH presentation, the median duration of response had not been reached. The same was true for progression-free survival and overall survival. The progression-free survival estimate for 12 months was 72.0%, and the overall survival estimate was 86.7%.

Treatment-emergent adverse events of any grade occurred in 96% of patients. The most frequent were neutropenia (43%), diarrhea (29%), nausea (29%), anemia (27%), fatigue (22%), pyrexia (20%), thrombocytopenia (19%), hyperphosphatemia (16%), vomiting (15%), and upper respiratory tract infection (15%). (About 22% of patients had neutropenia at baseline.)

The most frequent grade 3/4 adverse events were neutropenia (40%), anemia (18%), and thrombocytopenia (15%). Infections occurred in 72% of patients, with 20% of patients experiencing grade 3 or higher infections.

Serious adverse events occurred in 55% of patients, the most common being pyrexia (7%), autoimmune hemolytic anemia (7%), pneumonia (6%), and febrile neutropenia (5%).

Laboratory tumor lysis syndrome (TLS) occurred in 5 patients during the ramp-up period only. Two patients required a dose interruption of 1 day each. There were no clinical TLS events.

In the past, TLS has caused deaths in patients receiving venetoclax. In response, AbbVie stopped dose-escalation in patients receiving the drug and suspended enrollment in phase 1 trials.

However, researchers subsequently found that a modified dosing schedule, prophylaxis, and patient monitoring can reduce the risk of TLS.

Venetoclax is currently being evaluated in phase 3 trials for the treatment of relapsed, refractory, and previously untreated CLL.

Prescription medications

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has granted accelerated approval for venetoclax (Venclexta) to treat patients with chronic lymphocytic leukemia (CLL) who have 17p deletion and have received at least one prior therapy.

Venetoclax will be available in the US within about a week, according to the companies developing the drug, AbbVie and Genentech (a member of the

Roche Group).

The companies said they plan to offer patient assistance programs for qualifying patients who wish to receive venetoclax.

Venetoclax (formerly ABT-199) is the first FDA-approved treatment that targets the BCL-2 protein, which is overexpressed in many patients with CLL.

The drug is indicated for daily use after 17p deletion is confirmed via the FDA-approved companion diagnostic Vysis CLL FISH probe kit, which is manufactured by Abbott Molecular.

The FDA granted venetoclax accelerated approval rather than traditional approval because the drug has not yet shown a clinical benefit. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of venetoclax for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted venetoclax breakthrough therapy designation, priority review status, and orphan drug designation.

Phase 2 trial

Results from the pivotal phase 2 trial of venetoclax (M13-982, NCT01889186) were presented at the 2015 ASH Annual Meeting. According to those data, the trial enrolled 107 patients with relapsed or refractory CLL and 17p deletion.

Patients received venetoclax at 400 mg once daily following a weekly ramp-up schedule for the first 5 weeks. The primary endpoint was overall response rate, as determined by an independent review committee.

Eighty-five patients responded to treatment, for an overall response rate of 79.4%. Eight patients (7.5%) achieved a complete response or complete response with incomplete count recovery, 3 (2.8%) had a near partial response, and 74 (69.2%) had a partial response. Twenty-two patients (20.6%) did not respond.

As of the ASH presentation, the median duration of response had not been reached. The same was true for progression-free survival and overall survival. The progression-free survival estimate for 12 months was 72.0%, and the overall survival estimate was 86.7%.

Treatment-emergent adverse events of any grade occurred in 96% of patients. The most frequent were neutropenia (43%), diarrhea (29%), nausea (29%), anemia (27%), fatigue (22%), pyrexia (20%), thrombocytopenia (19%), hyperphosphatemia (16%), vomiting (15%), and upper respiratory tract infection (15%). (About 22% of patients had neutropenia at baseline.)

The most frequent grade 3/4 adverse events were neutropenia (40%), anemia (18%), and thrombocytopenia (15%). Infections occurred in 72% of patients, with 20% of patients experiencing grade 3 or higher infections.

Serious adverse events occurred in 55% of patients, the most common being pyrexia (7%), autoimmune hemolytic anemia (7%), pneumonia (6%), and febrile neutropenia (5%).

Laboratory tumor lysis syndrome (TLS) occurred in 5 patients during the ramp-up period only. Two patients required a dose interruption of 1 day each. There were no clinical TLS events.

In the past, TLS has caused deaths in patients receiving venetoclax. In response, AbbVie stopped dose-escalation in patients receiving the drug and suspended enrollment in phase 1 trials.

However, researchers subsequently found that a modified dosing schedule, prophylaxis, and patient monitoring can reduce the risk of TLS.

Venetoclax is currently being evaluated in phase 3 trials for the treatment of relapsed, refractory, and previously untreated CLL.

Researchers in the lab

Photo by Rhoda Baer

Researchers have established a public repository of leukemia and lymphoma xenografts, according to a report in Cancer Cell.

The repository, known as the Public Repository of Xenografts (PRoXe), contains material from bone marrow, peripheral blood, and lymph nodes of mice.

It also contains information on the patients from whom the cancer tissues were derived and details on the characteristics of the tumors themselves.

PRoXe is based at Dana-Farber Cancer Institute in Boston, Massachusetts, but it has a web portal that can be accessed by researchers around the world.

Those who register with PRoxE can access the repository and search for cells from patients with specific hematologic malignancies.

Researchers can then have frozen cells shipped to them and transplant the cells into mice to create patient-derived xenograft (PDX) models for testing drugs.

“About 90% of compounds that show anticancer activity in preclinical tests don’t work when given to patients,” said David Weinstock, MD, of the Dana-Farber Cancer Institute.

“By trying drugs in PDX models, we can ‘mimic’ large and expensive human clinical trials and get answers about efficacy more quickly, less expensively, and without the need for patients to get investigational drugs that won’t work.”

To demonstrate how PRoXe can be used, Dr Weinstock and his colleagues tested the MDM2 inhibitor CGM097 against B-cell acute lymphoblastic leukemia (B-ALL) in 2 groups of mice. One group had a mutation in the TP53 tumor suppressor gene, and the other did not.

The researchers observed superior survival in the mice with wild-type TP53. This result corresponds with the results of previous research, which showed that inhibitors that disrupt the MDM2-p53 interaction can be effective in tumor models and patient tumors with wild-type TP53.

Dr Weinstock and his colleagues said their results provide strong preclinical evidence for testing CGM097 in patients who have been extensively treated for B-ALL and have wild-type TP53.

Dr Weinstock also noted that the leaders of ProXe are negotiating with a number of academic centers in an attempt to incorporate their PDX models into the repository.

The Cancer Cell manuscript had 95 authors from 14 different centers that contributed samples, models, and/or effort to the project.

Researchers in the lab

Photo by Rhoda Baer

Researchers have established a public repository of leukemia and lymphoma xenografts, according to a report in Cancer Cell.

The repository, known as the Public Repository of Xenografts (PRoXe), contains material from bone marrow, peripheral blood, and lymph nodes of mice.

It also contains information on the patients from whom the cancer tissues were derived and details on the characteristics of the tumors themselves.

PRoXe is based at Dana-Farber Cancer Institute in Boston, Massachusetts, but it has a web portal that can be accessed by researchers around the world.

Those who register with PRoxE can access the repository and search for cells from patients with specific hematologic malignancies.

Researchers can then have frozen cells shipped to them and transplant the cells into mice to create patient-derived xenograft (PDX) models for testing drugs.

“About 90% of compounds that show anticancer activity in preclinical tests don’t work when given to patients,” said David Weinstock, MD, of the Dana-Farber Cancer Institute.

“By trying drugs in PDX models, we can ‘mimic’ large and expensive human clinical trials and get answers about efficacy more quickly, less expensively, and without the need for patients to get investigational drugs that won’t work.”

To demonstrate how PRoXe can be used, Dr Weinstock and his colleagues tested the MDM2 inhibitor CGM097 against B-cell acute lymphoblastic leukemia (B-ALL) in 2 groups of mice. One group had a mutation in the TP53 tumor suppressor gene, and the other did not.

The researchers observed superior survival in the mice with wild-type TP53. This result corresponds with the results of previous research, which showed that inhibitors that disrupt the MDM2-p53 interaction can be effective in tumor models and patient tumors with wild-type TP53.

Dr Weinstock and his colleagues said their results provide strong preclinical evidence for testing CGM097 in patients who have been extensively treated for B-ALL and have wild-type TP53.

Dr Weinstock also noted that the leaders of ProXe are negotiating with a number of academic centers in an attempt to incorporate their PDX models into the repository.

The Cancer Cell manuscript had 95 authors from 14 different centers that contributed samples, models, and/or effort to the project.

Researchers in the lab

Photo by Rhoda Baer

Researchers have established a public repository of leukemia and lymphoma xenografts, according to a report in Cancer Cell.

The repository, known as the Public Repository of Xenografts (PRoXe), contains material from bone marrow, peripheral blood, and lymph nodes of mice.

It also contains information on the patients from whom the cancer tissues were derived and details on the characteristics of the tumors themselves.

PRoXe is based at Dana-Farber Cancer Institute in Boston, Massachusetts, but it has a web portal that can be accessed by researchers around the world.

Those who register with PRoxE can access the repository and search for cells from patients with specific hematologic malignancies.

Researchers can then have frozen cells shipped to them and transplant the cells into mice to create patient-derived xenograft (PDX) models for testing drugs.

“About 90% of compounds that show anticancer activity in preclinical tests don’t work when given to patients,” said David Weinstock, MD, of the Dana-Farber Cancer Institute.

“By trying drugs in PDX models, we can ‘mimic’ large and expensive human clinical trials and get answers about efficacy more quickly, less expensively, and without the need for patients to get investigational drugs that won’t work.”

To demonstrate how PRoXe can be used, Dr Weinstock and his colleagues tested the MDM2 inhibitor CGM097 against B-cell acute lymphoblastic leukemia (B-ALL) in 2 groups of mice. One group had a mutation in the TP53 tumor suppressor gene, and the other did not.

The researchers observed superior survival in the mice with wild-type TP53. This result corresponds with the results of previous research, which showed that inhibitors that disrupt the MDM2-p53 interaction can be effective in tumor models and patient tumors with wild-type TP53.

Dr Weinstock and his colleagues said their results provide strong preclinical evidence for testing CGM097 in patients who have been extensively treated for B-ALL and have wild-type TP53.

Dr Weinstock also noted that the leaders of ProXe are negotiating with a number of academic centers in an attempt to incorporate their PDX models into the repository.

The Cancer Cell manuscript had 95 authors from 14 different centers that contributed samples, models, and/or effort to the project.

PET scan

Image by Jens Langner

Using PET imaging to guide chemotherapy can improve outcomes for patients with advanced Hodgkin lymphoma (HL), according to research published in the Journal of Clinical Oncology.

The study indicated that PET-guided treatment can improve progression-free survival (PFS) among patients who do not achieve remission with 2 cycles of ABVD.

The results also suggested the approach can spare some patients unnecessary toxicity.

“The goal of cancer treatment is to cure as many people as possible with as little toxicity as possible,” said study author Oliver Press, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

“We found a promising way to do that by tailoring treatment to Hodgkin patients, an approach which could lead to a new standard of care.”

Dr Press and his colleagues began this study with 358 HIV-negative patients with advanced HL, but only 336 of them were eligible and evaluable at baseline.

The patients’ median age was 32 (range, 18 to 60). Fifty-two percent had stage III disease, 48% had stage IV, 49% had an International Prognostic Score of 0 to 2, and 51% had a score of 3 to 7.

All of the patients received ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and underwent a PET scan to gauge their response after 2 cycles (PET2).

If the scan was negative, patients received a final 4 cycles of ABVD. If the scan was positive, patients received 6 cycles of eBEACOPP (escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone).

Central review of the PET2 scan was performed in 331 patients. Most (82%, n=271) had a negative scan.

Forty-nine of the 60 PET2-positive patients went on to receive eBEACOPP as planned, but 11 patients declined.

The median follow-up was 39.7 months. For the entire study cohort, the estimated 2-year overall survival was 98%, and the estimated 2-year PFS was 79%.

The 2-year estimated PFS was 82% for PET2-negative patients and 64% for PET2-positive patients. The researchers noted that, typically, if HL patients have a positive PET scan after 2 rounds of ABVD, their expected 2-year PFS ranges from about 15% to 30%.

The researchers also pointed out that eBEACOPP was significantly more toxic than ABVD. The incidence of grade 4/5 toxicities was 85.7% and 36.7%, respectively (P<0.001).

There were 3 treatment-related deaths—1 in the ABVD group and 2 in the eBEACOPP group. And 6 patients developed secondary malignancies—3 in each group—including 2 non-Hodgkin lymphomas, 2 kidney cancers, 1 melanoma, and 1 skin cancer.

“[O]nly 20% of the patients in our trial were exposed to eBEACOPP, which means [most patients] weren’t exposed to its bad effects,” said Jonathan Friedberg, MD, of the University of Rochester Medical Center in Rochester, New York.

“That’s important because many people diagnosed with Hodgkin lymphoma are in their 20s and 30s and want to have children. This response-adapted therapy would ensure that the people who need the more toxic drugs receive them and would spare others from infertility and serious toxicities.”

PET scan

Image by Jens Langner

Using PET imaging to guide chemotherapy can improve outcomes for patients with advanced Hodgkin lymphoma (HL), according to research published in the Journal of Clinical Oncology.

The study indicated that PET-guided treatment can improve progression-free survival (PFS) among patients who do not achieve remission with 2 cycles of ABVD.

The results also suggested the approach can spare some patients unnecessary toxicity.

“The goal of cancer treatment is to cure as many people as possible with as little toxicity as possible,” said study author Oliver Press, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

“We found a promising way to do that by tailoring treatment to Hodgkin patients, an approach which could lead to a new standard of care.”

Dr Press and his colleagues began this study with 358 HIV-negative patients with advanced HL, but only 336 of them were eligible and evaluable at baseline.

The patients’ median age was 32 (range, 18 to 60). Fifty-two percent had stage III disease, 48% had stage IV, 49% had an International Prognostic Score of 0 to 2, and 51% had a score of 3 to 7.

All of the patients received ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and underwent a PET scan to gauge their response after 2 cycles (PET2).

If the scan was negative, patients received a final 4 cycles of ABVD. If the scan was positive, patients received 6 cycles of eBEACOPP (escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone).

Central review of the PET2 scan was performed in 331 patients. Most (82%, n=271) had a negative scan.

Forty-nine of the 60 PET2-positive patients went on to receive eBEACOPP as planned, but 11 patients declined.

The median follow-up was 39.7 months. For the entire study cohort, the estimated 2-year overall survival was 98%, and the estimated 2-year PFS was 79%.

The 2-year estimated PFS was 82% for PET2-negative patients and 64% for PET2-positive patients. The researchers noted that, typically, if HL patients have a positive PET scan after 2 rounds of ABVD, their expected 2-year PFS ranges from about 15% to 30%.

The researchers also pointed out that eBEACOPP was significantly more toxic than ABVD. The incidence of grade 4/5 toxicities was 85.7% and 36.7%, respectively (P<0.001).

There were 3 treatment-related deaths—1 in the ABVD group and 2 in the eBEACOPP group. And 6 patients developed secondary malignancies—3 in each group—including 2 non-Hodgkin lymphomas, 2 kidney cancers, 1 melanoma, and 1 skin cancer.

“[O]nly 20% of the patients in our trial were exposed to eBEACOPP, which means [most patients] weren’t exposed to its bad effects,” said Jonathan Friedberg, MD, of the University of Rochester Medical Center in Rochester, New York.

“That’s important because many people diagnosed with Hodgkin lymphoma are in their 20s and 30s and want to have children. This response-adapted therapy would ensure that the people who need the more toxic drugs receive them and would spare others from infertility and serious toxicities.”

PET scan

Image by Jens Langner

Using PET imaging to guide chemotherapy can improve outcomes for patients with advanced Hodgkin lymphoma (HL), according to research published in the Journal of Clinical Oncology.

The study indicated that PET-guided treatment can improve progression-free survival (PFS) among patients who do not achieve remission with 2 cycles of ABVD.

The results also suggested the approach can spare some patients unnecessary toxicity.

“The goal of cancer treatment is to cure as many people as possible with as little toxicity as possible,” said study author Oliver Press, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

“We found a promising way to do that by tailoring treatment to Hodgkin patients, an approach which could lead to a new standard of care.”

Dr Press and his colleagues began this study with 358 HIV-negative patients with advanced HL, but only 336 of them were eligible and evaluable at baseline.

The patients’ median age was 32 (range, 18 to 60). Fifty-two percent had stage III disease, 48% had stage IV, 49% had an International Prognostic Score of 0 to 2, and 51% had a score of 3 to 7.

All of the patients received ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and underwent a PET scan to gauge their response after 2 cycles (PET2).

If the scan was negative, patients received a final 4 cycles of ABVD. If the scan was positive, patients received 6 cycles of eBEACOPP (escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone).

Central review of the PET2 scan was performed in 331 patients. Most (82%, n=271) had a negative scan.

Forty-nine of the 60 PET2-positive patients went on to receive eBEACOPP as planned, but 11 patients declined.

The median follow-up was 39.7 months. For the entire study cohort, the estimated 2-year overall survival was 98%, and the estimated 2-year PFS was 79%.

The 2-year estimated PFS was 82% for PET2-negative patients and 64% for PET2-positive patients. The researchers noted that, typically, if HL patients have a positive PET scan after 2 rounds of ABVD, their expected 2-year PFS ranges from about 15% to 30%.

The researchers also pointed out that eBEACOPP was significantly more toxic than ABVD. The incidence of grade 4/5 toxicities was 85.7% and 36.7%, respectively (P<0.001).

There were 3 treatment-related deaths—1 in the ABVD group and 2 in the eBEACOPP group. And 6 patients developed secondary malignancies—3 in each group—including 2 non-Hodgkin lymphomas, 2 kidney cancers, 1 melanoma, and 1 skin cancer.

“[O]nly 20% of the patients in our trial were exposed to eBEACOPP, which means [most patients] weren’t exposed to its bad effects,” said Jonathan Friedberg, MD, of the University of Rochester Medical Center in Rochester, New York.

“That’s important because many people diagnosed with Hodgkin lymphoma are in their 20s and 30s and want to have children. This response-adapted therapy would ensure that the people who need the more toxic drugs receive them and would spare others from infertility and serious toxicities.”

Bride and groom

Photo by Alena Kratochvilova

Results from two new studies provide a possible explanation for the link between marital status and survival in cancer patients.

Previous studies have shown that married cancer patients are more likely to survive and tend to have longer survival times than unmarried cancer patients.

Now, a pair of studies published in Cancer suggest it is the social support a patient receives from a spouse that may improve the patient’s outcome.

In the first study, Scarlett Lin Gomez, PhD, of the Cancer Prevention Institute of California, and her colleagues assessed the impact of socioeconomic factors and marital status on survival in cancer patients.

The team found evidence to suggest that economic resources play a minimal role in explaining the inferior survival observed in unmarried cancer patients.

In the second study, María Elena Martínez, PhD, of UC San Diego Moores Cancer Center, and her colleagues assessed the roles that race/ethnicity, sex, and nativity play in the survival of married and unmarried cancer patients.

The group found that not being married was associated with higher mortality, but the association varied by race/ethnicity and sex. The researchers believe these differences can be explained by the differences in social support networks between racial/ethnic groups and between men and women.

Patient cohort

Both studies were conducted on the same cohort of patients from the California Cancer Registry.

The researchers studied 783,167 cancer patients—393,470 males and 389,697 females. They were diagnosed from 2000 through 2009 with a first primary, invasive cancer of the 10 most common sites of cancer-related death for each sex, which included leukemias and lymphomas.

The patients were followed through December 31, 2012. A total of 386,607 patients died from any cause—204,007 males and 182,600 females.

Economic factors

Dr Gomez and her colleagues evaluated health insurance status and neighborhood socioeconomic status for the nearly 800,000 patients.

The researchers found that unmarried cancer patients had a greater risk of death than married patients, and this risk was higher among males than females. The hazard ratio (HR) for males was 1.27 (95% CI, 1.26-1.29), and the HR for females was 1.19 (95% CI, 1.18-1.20, P-interaction <0.001).

When the researchers adjusted for insurance status and neighborhood socioeconomic status, the marital status HRs decreased to 1.22 (95% CI, 1.21–1.24) for males and 1.15 (95% CI, 1.14–1.16) for females.

Based on these results, the researchers concluded that the survival benefit of marriage operates independently of the economic resources evaluated in this study.

“While other studies have found similar protective effects associated with being married, ours is the first in a large, population-based setting to assess the extent to which economic resources explain these protective effects,” Dr Gomez said. “Our study provides evidence for social support as a key driver.”

Race/ethnicity, nativity, and sex

Dr Martínez and her colleagues found that all-cause mortality was higher in the unmarried patients than in the married patients, but this varied significantly according to race/ethnicity and sex.

Marriage conferred less of a survival benefit for women than for men. However, for both sexes, non-Hispanic whites benefitted the most from being married, and Hispanics and Asian Pacific Islanders benefitted less.

Among males, the adjusted HRs were 1.24 (95% CI, 1.23-1.26) in non-Hispanic whites, 1.20 (95% CI, 1.16-1.24) in blacks, 1.20 (95% CI, 1.17-1.23) in Hispanics, and 1.11 (95% CI, 1.07-1.15) in Asian Pacific Islanders.

In females, the adjusted HRs were 1.17 (95% CI, 1.15-1.18) in non-Hispanic whites, 1.09 (95% CI, 1.05-1.13) in blacks, 1.11 (95% CI, 1.08-1.14) in Hispanics, and 1.07 (95% CI, 1.04-1.11) in Asian Pacific Islanders.

The researchers also found that all-cause mortality associated with unmarried status was higher in US-born Asian Pacific Islander and Hispanic men and women relative to their foreign-born counterparts.

“The results suggest that the more acculturated you become to US culture, the more it impacts cancer survivorship,” Dr Martínez said. “Our hypothesis is that non-Hispanic whites don’t have the same social network as other cultures that have stronger bonds with family and friends outside of marriage.”

“As individuals acculturate, they tend to lose those bonds. It’s also been shown that women seek out help for health concerns more frequently than men, and women tend to remind spouses to see their physicians and live a healthy lifestyle.”

Bride and groom

Photo by Alena Kratochvilova

Results from two new studies provide a possible explanation for the link between marital status and survival in cancer patients.

Previous studies have shown that married cancer patients are more likely to survive and tend to have longer survival times than unmarried cancer patients.

Now, a pair of studies published in Cancer suggest it is the social support a patient receives from a spouse that may improve the patient’s outcome.

In the first study, Scarlett Lin Gomez, PhD, of the Cancer Prevention Institute of California, and her colleagues assessed the impact of socioeconomic factors and marital status on survival in cancer patients.

The team found evidence to suggest that economic resources play a minimal role in explaining the inferior survival observed in unmarried cancer patients.

In the second study, María Elena Martínez, PhD, of UC San Diego Moores Cancer Center, and her colleagues assessed the roles that race/ethnicity, sex, and nativity play in the survival of married and unmarried cancer patients.

The group found that not being married was associated with higher mortality, but the association varied by race/ethnicity and sex. The researchers believe these differences can be explained by the differences in social support networks between racial/ethnic groups and between men and women.

Patient cohort

Both studies were conducted on the same cohort of patients from the California Cancer Registry.

The researchers studied 783,167 cancer patients—393,470 males and 389,697 females. They were diagnosed from 2000 through 2009 with a first primary, invasive cancer of the 10 most common sites of cancer-related death for each sex, which included leukemias and lymphomas.

The patients were followed through December 31, 2012. A total of 386,607 patients died from any cause—204,007 males and 182,600 females.

Economic factors

Dr Gomez and her colleagues evaluated health insurance status and neighborhood socioeconomic status for the nearly 800,000 patients.

The researchers found that unmarried cancer patients had a greater risk of death than married patients, and this risk was higher among males than females. The hazard ratio (HR) for males was 1.27 (95% CI, 1.26-1.29), and the HR for females was 1.19 (95% CI, 1.18-1.20, P-interaction <0.001).

When the researchers adjusted for insurance status and neighborhood socioeconomic status, the marital status HRs decreased to 1.22 (95% CI, 1.21–1.24) for males and 1.15 (95% CI, 1.14–1.16) for females.

Based on these results, the researchers concluded that the survival benefit of marriage operates independently of the economic resources evaluated in this study.

“While other studies have found similar protective effects associated with being married, ours is the first in a large, population-based setting to assess the extent to which economic resources explain these protective effects,” Dr Gomez said. “Our study provides evidence for social support as a key driver.”

Race/ethnicity, nativity, and sex

Dr Martínez and her colleagues found that all-cause mortality was higher in the unmarried patients than in the married patients, but this varied significantly according to race/ethnicity and sex.

Marriage conferred less of a survival benefit for women than for men. However, for both sexes, non-Hispanic whites benefitted the most from being married, and Hispanics and Asian Pacific Islanders benefitted less.

Among males, the adjusted HRs were 1.24 (95% CI, 1.23-1.26) in non-Hispanic whites, 1.20 (95% CI, 1.16-1.24) in blacks, 1.20 (95% CI, 1.17-1.23) in Hispanics, and 1.11 (95% CI, 1.07-1.15) in Asian Pacific Islanders.

In females, the adjusted HRs were 1.17 (95% CI, 1.15-1.18) in non-Hispanic whites, 1.09 (95% CI, 1.05-1.13) in blacks, 1.11 (95% CI, 1.08-1.14) in Hispanics, and 1.07 (95% CI, 1.04-1.11) in Asian Pacific Islanders.

The researchers also found that all-cause mortality associated with unmarried status was higher in US-born Asian Pacific Islander and Hispanic men and women relative to their foreign-born counterparts.

“The results suggest that the more acculturated you become to US culture, the more it impacts cancer survivorship,” Dr Martínez said. “Our hypothesis is that non-Hispanic whites don’t have the same social network as other cultures that have stronger bonds with family and friends outside of marriage.”

“As individuals acculturate, they tend to lose those bonds. It’s also been shown that women seek out help for health concerns more frequently than men, and women tend to remind spouses to see their physicians and live a healthy lifestyle.”

Bride and groom

Photo by Alena Kratochvilova

Results from two new studies provide a possible explanation for the link between marital status and survival in cancer patients.

Previous studies have shown that married cancer patients are more likely to survive and tend to have longer survival times than unmarried cancer patients.

Now, a pair of studies published in Cancer suggest it is the social support a patient receives from a spouse that may improve the patient’s outcome.

In the first study, Scarlett Lin Gomez, PhD, of the Cancer Prevention Institute of California, and her colleagues assessed the impact of socioeconomic factors and marital status on survival in cancer patients.

The team found evidence to suggest that economic resources play a minimal role in explaining the inferior survival observed in unmarried cancer patients.

In the second study, María Elena Martínez, PhD, of UC San Diego Moores Cancer Center, and her colleagues assessed the roles that race/ethnicity, sex, and nativity play in the survival of married and unmarried cancer patients.

The group found that not being married was associated with higher mortality, but the association varied by race/ethnicity and sex. The researchers believe these differences can be explained by the differences in social support networks between racial/ethnic groups and between men and women.

Patient cohort

Both studies were conducted on the same cohort of patients from the California Cancer Registry.

The researchers studied 783,167 cancer patients—393,470 males and 389,697 females. They were diagnosed from 2000 through 2009 with a first primary, invasive cancer of the 10 most common sites of cancer-related death for each sex, which included leukemias and lymphomas.

The patients were followed through December 31, 2012. A total of 386,607 patients died from any cause—204,007 males and 182,600 females.

Economic factors

Dr Gomez and her colleagues evaluated health insurance status and neighborhood socioeconomic status for the nearly 800,000 patients.

The researchers found that unmarried cancer patients had a greater risk of death than married patients, and this risk was higher among males than females. The hazard ratio (HR) for males was 1.27 (95% CI, 1.26-1.29), and the HR for females was 1.19 (95% CI, 1.18-1.20, P-interaction <0.001).

When the researchers adjusted for insurance status and neighborhood socioeconomic status, the marital status HRs decreased to 1.22 (95% CI, 1.21–1.24) for males and 1.15 (95% CI, 1.14–1.16) for females.

Based on these results, the researchers concluded that the survival benefit of marriage operates independently of the economic resources evaluated in this study.

“While other studies have found similar protective effects associated with being married, ours is the first in a large, population-based setting to assess the extent to which economic resources explain these protective effects,” Dr Gomez said. “Our study provides evidence for social support as a key driver.”

Race/ethnicity, nativity, and sex

Dr Martínez and her colleagues found that all-cause mortality was higher in the unmarried patients than in the married patients, but this varied significantly according to race/ethnicity and sex.

Marriage conferred less of a survival benefit for women than for men. However, for both sexes, non-Hispanic whites benefitted the most from being married, and Hispanics and Asian Pacific Islanders benefitted less.

Among males, the adjusted HRs were 1.24 (95% CI, 1.23-1.26) in non-Hispanic whites, 1.20 (95% CI, 1.16-1.24) in blacks, 1.20 (95% CI, 1.17-1.23) in Hispanics, and 1.11 (95% CI, 1.07-1.15) in Asian Pacific Islanders.

In females, the adjusted HRs were 1.17 (95% CI, 1.15-1.18) in non-Hispanic whites, 1.09 (95% CI, 1.05-1.13) in blacks, 1.11 (95% CI, 1.08-1.14) in Hispanics, and 1.07 (95% CI, 1.04-1.11) in Asian Pacific Islanders.

The researchers also found that all-cause mortality associated with unmarried status was higher in US-born Asian Pacific Islander and Hispanic men and women relative to their foreign-born counterparts.

“The results suggest that the more acculturated you become to US culture, the more it impacts cancer survivorship,” Dr Martínez said. “Our hypothesis is that non-Hispanic whites don’t have the same social network as other cultures that have stronger bonds with family and friends outside of marriage.”

“As individuals acculturate, they tend to lose those bonds. It’s also been shown that women seek out help for health concerns more frequently than men, and women tend to remind spouses to see their physicians and live a healthy lifestyle.”

As a single agent for use in patients with lymphoma, an acceptable once-daily dose of OTX015 appears to be 80 mg on a 14 days on, 7 days off schedule, the results of a phase 1 study indicate.

The small-molecule inhibitor, which inhibits binding of bromodomain and exterminal proteins to acetylated histones, was associated with acceptable toxicity and efficacy in this regimen. The investigational drug is now being tested in expansion cohorts on a schedule of 14 days every 3 weeks, a regimen projected to allow for recovery from the drug’s toxic effects, Dr. Sandy Amorin of Hôpital Saint Louis, Paris, and associates reported.

The drug also is being evaluated in patients with acute leukemias.

Adults with nonleukemia hematologic malignancies that progressed on standard therapies participated in the open-label study, which was conducted at seven university hospital centers in Europe. Oral OTX015 was given once a day at one of five doses (10 mg, 20 mg, 40 mg, 80 mg, and 120 mg). The 3 + 3 study design permitted evaluation of alternative administration schedules. The primary endpoint was dose-limiting toxicity in the first treatment cycle (21 days). Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity of OTX015. The study is ongoing and is registered with ClinicalTrials.gov, number NCT01713582.

The study included 33 patients with lymphoma and 12 with myeloma; patients’ median age was 66 years, and they had received a median of four lines of prior therapy. No dose-limiting toxicities were seen in three patients given doses as high as 80 mg once a day. However, grade 4 thrombocytopenia occurred in five of six patients on a 21-day schedule of 40 mg twice a day. No patient tolerated various schedules of 120 mg once a day (Lancet Haematol. 2016;3[4]:e196-204).

The researchers then examined the 80 mg once a day dose on a continuous basis in four patients, two of whom developed grade 4 thrombocytopenia. In light of these and other toxicities, a regimen was proposed of 80 mg once a day on a schedule of 14 days on, 7 days off.

Thrombocytopenia affected 43 of 45 patients, and 26 of them had grade 3-4 events. Other grade 3-4 events were infrequent. Anemia was seen in 41, and neutropenia in 23.

Of three patients with diffuse large B-cell lymphoma, two had complete responses at 120 mg once a day, and one had a partial response at 80 mg once a day. Six additional patients, two with diffuse large B-cell lymphoma and four with indolent lymphomas, had evidence of clinical activity, but did not meet the criteria for an objective response.

The study was funded by the developers of OTX015, Oncoethix GmbH, a wholly owned subsidiary of Merck Sharp & Dohme.

mdales@frontlinemedcom.com

On Twitter @maryjodales

As a single agent for use in patients with lymphoma, an acceptable once-daily dose of OTX015 appears to be 80 mg on a 14 days on, 7 days off schedule, the results of a phase 1 study indicate.

The small-molecule inhibitor, which inhibits binding of bromodomain and exterminal proteins to acetylated histones, was associated with acceptable toxicity and efficacy in this regimen. The investigational drug is now being tested in expansion cohorts on a schedule of 14 days every 3 weeks, a regimen projected to allow for recovery from the drug’s toxic effects, Dr. Sandy Amorin of Hôpital Saint Louis, Paris, and associates reported.

The drug also is being evaluated in patients with acute leukemias.

Adults with nonleukemia hematologic malignancies that progressed on standard therapies participated in the open-label study, which was conducted at seven university hospital centers in Europe. Oral OTX015 was given once a day at one of five doses (10 mg, 20 mg, 40 mg, 80 mg, and 120 mg). The 3 + 3 study design permitted evaluation of alternative administration schedules. The primary endpoint was dose-limiting toxicity in the first treatment cycle (21 days). Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity of OTX015. The study is ongoing and is registered with ClinicalTrials.gov, number NCT01713582.

The study included 33 patients with lymphoma and 12 with myeloma; patients’ median age was 66 years, and they had received a median of four lines of prior therapy. No dose-limiting toxicities were seen in three patients given doses as high as 80 mg once a day. However, grade 4 thrombocytopenia occurred in five of six patients on a 21-day schedule of 40 mg twice a day. No patient tolerated various schedules of 120 mg once a day (Lancet Haematol. 2016;3[4]:e196-204).

The researchers then examined the 80 mg once a day dose on a continuous basis in four patients, two of whom developed grade 4 thrombocytopenia. In light of these and other toxicities, a regimen was proposed of 80 mg once a day on a schedule of 14 days on, 7 days off.

Thrombocytopenia affected 43 of 45 patients, and 26 of them had grade 3-4 events. Other grade 3-4 events were infrequent. Anemia was seen in 41, and neutropenia in 23.

Of three patients with diffuse large B-cell lymphoma, two had complete responses at 120 mg once a day, and one had a partial response at 80 mg once a day. Six additional patients, two with diffuse large B-cell lymphoma and four with indolent lymphomas, had evidence of clinical activity, but did not meet the criteria for an objective response.

The study was funded by the developers of OTX015, Oncoethix GmbH, a wholly owned subsidiary of Merck Sharp & Dohme.

mdales@frontlinemedcom.com

On Twitter @maryjodales

As a single agent for use in patients with lymphoma, an acceptable once-daily dose of OTX015 appears to be 80 mg on a 14 days on, 7 days off schedule, the results of a phase 1 study indicate.

The small-molecule inhibitor, which inhibits binding of bromodomain and exterminal proteins to acetylated histones, was associated with acceptable toxicity and efficacy in this regimen. The investigational drug is now being tested in expansion cohorts on a schedule of 14 days every 3 weeks, a regimen projected to allow for recovery from the drug’s toxic effects, Dr. Sandy Amorin of Hôpital Saint Louis, Paris, and associates reported.

The drug also is being evaluated in patients with acute leukemias.

Adults with nonleukemia hematologic malignancies that progressed on standard therapies participated in the open-label study, which was conducted at seven university hospital centers in Europe. Oral OTX015 was given once a day at one of five doses (10 mg, 20 mg, 40 mg, 80 mg, and 120 mg). The 3 + 3 study design permitted evaluation of alternative administration schedules. The primary endpoint was dose-limiting toxicity in the first treatment cycle (21 days). Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity of OTX015. The study is ongoing and is registered with ClinicalTrials.gov, number NCT01713582.

The study included 33 patients with lymphoma and 12 with myeloma; patients’ median age was 66 years, and they had received a median of four lines of prior therapy. No dose-limiting toxicities were seen in three patients given doses as high as 80 mg once a day. However, grade 4 thrombocytopenia occurred in five of six patients on a 21-day schedule of 40 mg twice a day. No patient tolerated various schedules of 120 mg once a day (Lancet Haematol. 2016;3[4]:e196-204).

The researchers then examined the 80 mg once a day dose on a continuous basis in four patients, two of whom developed grade 4 thrombocytopenia. In light of these and other toxicities, a regimen was proposed of 80 mg once a day on a schedule of 14 days on, 7 days off.

Thrombocytopenia affected 43 of 45 patients, and 26 of them had grade 3-4 events. Other grade 3-4 events were infrequent. Anemia was seen in 41, and neutropenia in 23.

Of three patients with diffuse large B-cell lymphoma, two had complete responses at 120 mg once a day, and one had a partial response at 80 mg once a day. Six additional patients, two with diffuse large B-cell lymphoma and four with indolent lymphomas, had evidence of clinical activity, but did not meet the criteria for an objective response.

The study was funded by the developers of OTX015, Oncoethix GmbH, a wholly owned subsidiary of Merck Sharp & Dohme.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Chemotherapy drugs

Photo by Bill Branson

Long-term results of the HD2000 trial reveal similar survival rates in patients with previously untreated, aggressive Hodgkin lymphoma (HL) who received 3 different combination treatment regimens.

At 10 years of follow-up, there was no significant difference in overall survival (OS) or progression-free survival (PFS) whether patients received ABVD, BEACOPP, or CEC.

However, patients who received ABVD were significantly less likely than those who received BEACOPP or CEC to develop second malignancies.

Francesco Merli, MD, of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) in Italy, and his colleagues reported these results in the Journal of Clinical Oncology.

The trial enrolled 307 patients with advanced-stage HL. Patients were randomized to receive 1 of 3 treatment regimens:

• Six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine)
• Four escalated plus 2 standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)
• Six cycles of CEC (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin).

Some patients also received radiotherapy, but there was no significant difference in the proportion of patients receiving radiotherapy across the treatment arms—46% in the ABVD arm, 44% in the BEACOPP arm, and 43% in the CEC arm (P=0.871).

Results

At the end of all therapy, the complete response rate was 84% with ABVD, 91% with BEACOPP, and 83% with CEC.

There were 84 patients who did not achieve a complete response, and salvage data were available for 73 of these patients. Three patients (4%) died before salvage therapy could begin, 26 (36%) received conventional chemotherapy, 40 (55%) received a hematopoietic stem cell transplant, and 4 (5%) received radiotherapy.

The median follow-up was 120 months (range, 4 to 169 months), and 295 patients were evaluable.

In a previous analysis, at a median follow-up of 42 months, patients who received BEACOPP had superior PFS compared to patients who received ABVD.

However, in the current analysis, there was no significant difference in PFS between the 3 treatment arms. The 10-year PFS was 69% in the ABVD arm, 75% in the BEACOPP arm, and 76% in the CEC arm (P=0.471).

Likewise, there was no significant difference in OS between the treatment arms. The 10-year OS was 85% in the ABVD arm, 84% in the BEACOPP arm, and 86% in the CEC arm (P=0.892).

There were a total of 13 second malignancies—1 in the ABVD arm and 6 each in the BEACOPP and CEC arms.

The cumulative risk of developing a second malignancy at 10 years was 0.9% in the ABVD arm, 6.6% in the BEACOPP arm, and 6% in the CEC arm. So the risk with either BEACOPP or CEC was significantly higher than with ABVD (P=0.027 and 0.02, respectively).

The researchers said these results suggest BEACOPP provides better disease control than ABVD, but this benefit is counterbalanced by a higher rate of late major events with BEACOPP, particularly second malignancies, which resulted in patient deaths.

So the team concluded that BEACOPP is a viable treatment option for advanced HL, but it should not be considered the standard for all patients because 70% of these patients may be cured with ABVD and limited radiotherapy. A careful assessment of the risk-benefit ratio of the initial treatment choice is warranted.

Chemotherapy drugs

Photo by Bill Branson

Long-term results of the HD2000 trial reveal similar survival rates in patients with previously untreated, aggressive Hodgkin lymphoma (HL) who received 3 different combination treatment regimens.

At 10 years of follow-up, there was no significant difference in overall survival (OS) or progression-free survival (PFS) whether patients received ABVD, BEACOPP, or CEC.

However, patients who received ABVD were significantly less likely than those who received BEACOPP or CEC to develop second malignancies.

Francesco Merli, MD, of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) in Italy, and his colleagues reported these results in the Journal of Clinical Oncology.

The trial enrolled 307 patients with advanced-stage HL. Patients were randomized to receive 1 of 3 treatment regimens:

• Six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine)
• Four escalated plus 2 standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)
• Six cycles of CEC (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin).

Some patients also received radiotherapy, but there was no significant difference in the proportion of patients receiving radiotherapy across the treatment arms—46% in the ABVD arm, 44% in the BEACOPP arm, and 43% in the CEC arm (P=0.871).

Results

At the end of all therapy, the complete response rate was 84% with ABVD, 91% with BEACOPP, and 83% with CEC.

There were 84 patients who did not achieve a complete response, and salvage data were available for 73 of these patients. Three patients (4%) died before salvage therapy could begin, 26 (36%) received conventional chemotherapy, 40 (55%) received a hematopoietic stem cell transplant, and 4 (5%) received radiotherapy.

The median follow-up was 120 months (range, 4 to 169 months), and 295 patients were evaluable.

In a previous analysis, at a median follow-up of 42 months, patients who received BEACOPP had superior PFS compared to patients who received ABVD.

However, in the current analysis, there was no significant difference in PFS between the 3 treatment arms. The 10-year PFS was 69% in the ABVD arm, 75% in the BEACOPP arm, and 76% in the CEC arm (P=0.471).

Likewise, there was no significant difference in OS between the treatment arms. The 10-year OS was 85% in the ABVD arm, 84% in the BEACOPP arm, and 86% in the CEC arm (P=0.892).

There were a total of 13 second malignancies—1 in the ABVD arm and 6 each in the BEACOPP and CEC arms.

The cumulative risk of developing a second malignancy at 10 years was 0.9% in the ABVD arm, 6.6% in the BEACOPP arm, and 6% in the CEC arm. So the risk with either BEACOPP or CEC was significantly higher than with ABVD (P=0.027 and 0.02, respectively).

The researchers said these results suggest BEACOPP provides better disease control than ABVD, but this benefit is counterbalanced by a higher rate of late major events with BEACOPP, particularly second malignancies, which resulted in patient deaths.

So the team concluded that BEACOPP is a viable treatment option for advanced HL, but it should not be considered the standard for all patients because 70% of these patients may be cured with ABVD and limited radiotherapy. A careful assessment of the risk-benefit ratio of the initial treatment choice is warranted.

Chemotherapy drugs

Photo by Bill Branson

Long-term results of the HD2000 trial reveal similar survival rates in patients with previously untreated, aggressive Hodgkin lymphoma (HL) who received 3 different combination treatment regimens.

At 10 years of follow-up, there was no significant difference in overall survival (OS) or progression-free survival (PFS) whether patients received ABVD, BEACOPP, or CEC.

However, patients who received ABVD were significantly less likely than those who received BEACOPP or CEC to develop second malignancies.

Francesco Merli, MD, of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) in Italy, and his colleagues reported these results in the Journal of Clinical Oncology.

The trial enrolled 307 patients with advanced-stage HL. Patients were randomized to receive 1 of 3 treatment regimens:

• Six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine)
• Four escalated plus 2 standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)
• Six cycles of CEC (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin).

Some patients also received radiotherapy, but there was no significant difference in the proportion of patients receiving radiotherapy across the treatment arms—46% in the ABVD arm, 44% in the BEACOPP arm, and 43% in the CEC arm (P=0.871).

Results

At the end of all therapy, the complete response rate was 84% with ABVD, 91% with BEACOPP, and 83% with CEC.

There were 84 patients who did not achieve a complete response, and salvage data were available for 73 of these patients. Three patients (4%) died before salvage therapy could begin, 26 (36%) received conventional chemotherapy, 40 (55%) received a hematopoietic stem cell transplant, and 4 (5%) received radiotherapy.

The median follow-up was 120 months (range, 4 to 169 months), and 295 patients were evaluable.

In a previous analysis, at a median follow-up of 42 months, patients who received BEACOPP had superior PFS compared to patients who received ABVD.

However, in the current analysis, there was no significant difference in PFS between the 3 treatment arms. The 10-year PFS was 69% in the ABVD arm, 75% in the BEACOPP arm, and 76% in the CEC arm (P=0.471).

Likewise, there was no significant difference in OS between the treatment arms. The 10-year OS was 85% in the ABVD arm, 84% in the BEACOPP arm, and 86% in the CEC arm (P=0.892).

There were a total of 13 second malignancies—1 in the ABVD arm and 6 each in the BEACOPP and CEC arms.

The cumulative risk of developing a second malignancy at 10 years was 0.9% in the ABVD arm, 6.6% in the BEACOPP arm, and 6% in the CEC arm. So the risk with either BEACOPP or CEC was significantly higher than with ABVD (P=0.027 and 0.02, respectively).

The researchers said these results suggest BEACOPP provides better disease control than ABVD, but this benefit is counterbalanced by a higher rate of late major events with BEACOPP, particularly second malignancies, which resulted in patient deaths.

So the team concluded that BEACOPP is a viable treatment option for advanced HL, but it should not be considered the standard for all patients because 70% of these patients may be cured with ABVD and limited radiotherapy. A careful assessment of the risk-benefit ratio of the initial treatment choice is warranted.

Renal status should be evaluated at diagnosis and follow-up in all myeloma patients, according to new guidance from the International Myeloma Working Group published online in the Journal of Clinical Oncology.

Renal impairment (RI) affects up to half of patients with multiple myeloma, and severe RI predicts early death, noted Dr. Meletios Dimopoulos of National and Kapodistrian University of Athens and his associates. Novel therapies have substantially increased survival for myeloma with less severe kidney disease, underscoring the importance of early treatment. To develop the guidelines, the authors reviewed all evidence from randomized trials, systematic reviews, meta-analyses, and prospective and observational studies published through December 2015 (J Clin Oncol. 2016 Mar 14. doi: 10.1200/JCO.2015.65.0044).

Grade A recommendations (evidence obtained from meta-analysis of multiple well-designed, randomized controlled trials) include the following:

Evaluate serum creatinine, estimated glomerular filtration rate, and electrolytes at initial diagnosis and follow-up assessments. Also perform the serum free light chain test, if available, and electrophoresis of a 24-hour urine specimen.

In patients with stabilized serum creatinine, evaluate GFR using the Chronic Kidney Disease Epidemiology Collaboration (preferred) or the Modification of Diet in Renal Disease formulas.

Based on GFR, determine stage of chronic kidney disease (ranging from 1, kidney damage with normal or elevated GFR, to 5, renal failure).

Bortezomib remains the foundational treatment for myeloma-related renal impairment, the authors emphasized. This 26S proteasome inhibitor should be started at the standard dose of 1.3 mg/m² on days 1, 4, 8, and 11 of a 3-week cycle.

Another option for patients with creatinine clearance above 15 mL/min is carfilzomib, which needs no dose modification and yields similar results regardless of RI status. However, more data are needed on its renal safety, the authors said.

Patients with creatinine clearance above 30 mL/min can safely receive ixazomib in combination with lenalidomide and dexamethasone.

Those with creatinine clearance above 45 mL/min should receive pomalidomide at a dose of 4 mg/day; it is not yet clear whether the dose should be cut for more severe renal impairment.

Hypercalcemia can be treated with bisphosphonates, but patients with creatinine clearance below 30 mL/min should not receive pamidronate or zoledronic acid.

Avoid nephrotoxic agents, such as as aminoglycosides, furosemide, and contrast agents, in all patients with multiple myeloma and RI.

Dr. Dimopoulos reported receiving honoraria or financial support related to travel, accommodations, or expenses from Amgen, Celgene, Onyx Pharmaceuticals, Janssen-Cilag, Bristol-Myers Squibb, Novartis, and Genesis Pharmaceuticals. Seventeen coauthors also reported financial relationships with a number of pharmaceutical companies. The remaining three coauthors had no disclosures.

Renal status should be evaluated at diagnosis and follow-up in all myeloma patients, according to new guidance from the International Myeloma Working Group published online in the Journal of Clinical Oncology.

Renal impairment (RI) affects up to half of patients with multiple myeloma, and severe RI predicts early death, noted Dr. Meletios Dimopoulos of National and Kapodistrian University of Athens and his associates. Novel therapies have substantially increased survival for myeloma with less severe kidney disease, underscoring the importance of early treatment. To develop the guidelines, the authors reviewed all evidence from randomized trials, systematic reviews, meta-analyses, and prospective and observational studies published through December 2015 (J Clin Oncol. 2016 Mar 14. doi: 10.1200/JCO.2015.65.0044).

Grade A recommendations (evidence obtained from meta-analysis of multiple well-designed, randomized controlled trials) include the following:

Evaluate serum creatinine, estimated glomerular filtration rate, and electrolytes at initial diagnosis and follow-up assessments. Also perform the serum free light chain test, if available, and electrophoresis of a 24-hour urine specimen.

In patients with stabilized serum creatinine, evaluate GFR using the Chronic Kidney Disease Epidemiology Collaboration (preferred) or the Modification of Diet in Renal Disease formulas.

Based on GFR, determine stage of chronic kidney disease (ranging from 1, kidney damage with normal or elevated GFR, to 5, renal failure).

Bortezomib remains the foundational treatment for myeloma-related renal impairment, the authors emphasized. This 26S proteasome inhibitor should be started at the standard dose of 1.3 mg/m² on days 1, 4, 8, and 11 of a 3-week cycle.

Another option for patients with creatinine clearance above 15 mL/min is carfilzomib, which needs no dose modification and yields similar results regardless of RI status. However, more data are needed on its renal safety, the authors said.

Patients with creatinine clearance above 30 mL/min can safely receive ixazomib in combination with lenalidomide and dexamethasone.

Those with creatinine clearance above 45 mL/min should receive pomalidomide at a dose of 4 mg/day; it is not yet clear whether the dose should be cut for more severe renal impairment.

Hypercalcemia can be treated with bisphosphonates, but patients with creatinine clearance below 30 mL/min should not receive pamidronate or zoledronic acid.

Avoid nephrotoxic agents, such as as aminoglycosides, furosemide, and contrast agents, in all patients with multiple myeloma and RI.

Dr. Dimopoulos reported receiving honoraria or financial support related to travel, accommodations, or expenses from Amgen, Celgene, Onyx Pharmaceuticals, Janssen-Cilag, Bristol-Myers Squibb, Novartis, and Genesis Pharmaceuticals. Seventeen coauthors also reported financial relationships with a number of pharmaceutical companies. The remaining three coauthors had no disclosures.

Renal status should be evaluated at diagnosis and follow-up in all myeloma patients, according to new guidance from the International Myeloma Working Group published online in the Journal of Clinical Oncology.

Renal impairment (RI) affects up to half of patients with multiple myeloma, and severe RI predicts early death, noted Dr. Meletios Dimopoulos of National and Kapodistrian University of Athens and his associates. Novel therapies have substantially increased survival for myeloma with less severe kidney disease, underscoring the importance of early treatment. To develop the guidelines, the authors reviewed all evidence from randomized trials, systematic reviews, meta-analyses, and prospective and observational studies published through December 2015 (J Clin Oncol. 2016 Mar 14. doi: 10.1200/JCO.2015.65.0044).

Grade A recommendations (evidence obtained from meta-analysis of multiple well-designed, randomized controlled trials) include the following:

Evaluate serum creatinine, estimated glomerular filtration rate, and electrolytes at initial diagnosis and follow-up assessments. Also perform the serum free light chain test, if available, and electrophoresis of a 24-hour urine specimen.

In patients with stabilized serum creatinine, evaluate GFR using the Chronic Kidney Disease Epidemiology Collaboration (preferred) or the Modification of Diet in Renal Disease formulas.

Based on GFR, determine stage of chronic kidney disease (ranging from 1, kidney damage with normal or elevated GFR, to 5, renal failure).

Bortezomib remains the foundational treatment for myeloma-related renal impairment, the authors emphasized. This 26S proteasome inhibitor should be started at the standard dose of 1.3 mg/m² on days 1, 4, 8, and 11 of a 3-week cycle.

Another option for patients with creatinine clearance above 15 mL/min is carfilzomib, which needs no dose modification and yields similar results regardless of RI status. However, more data are needed on its renal safety, the authors said.

Patients with creatinine clearance above 30 mL/min can safely receive ixazomib in combination with lenalidomide and dexamethasone.

Those with creatinine clearance above 45 mL/min should receive pomalidomide at a dose of 4 mg/day; it is not yet clear whether the dose should be cut for more severe renal impairment.

Hypercalcemia can be treated with bisphosphonates, but patients with creatinine clearance below 30 mL/min should not receive pamidronate or zoledronic acid.

Avoid nephrotoxic agents, such as as aminoglycosides, furosemide, and contrast agents, in all patients with multiple myeloma and RI.

Dr. Dimopoulos reported receiving honoraria or financial support related to travel, accommodations, or expenses from Amgen, Celgene, Onyx Pharmaceuticals, Janssen-Cilag, Bristol-Myers Squibb, Novartis, and Genesis Pharmaceuticals. Seventeen coauthors also reported financial relationships with a number of pharmaceutical companies. The remaining three coauthors had no disclosures.

 

 

Micrograph showing DLBCL

 

The small-molecule inhibitor CUDC-907 can provide disease control in patients with relapsed or refractory lymphoma and multiple myeloma (MM), according to researchers.

In a phase 1 trial, CUDC-907 produced responses in a small number of patients with diffuse large B-cell lymphoma (DLBCL).

And more than half of patients had stable disease while on CUDC-907, including those with MM, DLBCL, Hodgkin lymphoma (HL), and other lymphomas.

However, a majority of patients in this trial—84%—discontinued treatment due to confirmed progressive disease or signs of progression.

These results were published in The Lancet. The trial was sponsored by Curis, Inc., the company developing CUDC-907, and the Leukemia and Lymphoma Society.

“The data from the phase 1 monotherapy trial for CUDC-907, especially in heavily pretreated patients with relapsed/refractory DLBCL are very encouraging, and we look forward to data emerging from the current phase 2 trial in patients with MYC-altered DLBCL,” said study author Anas Younes, MD, of the Memorial Sloan Kettering Cancer Center in New York, New York.

CUDC-907 is an oral, dual inhibitor of class I and II histone deacetylases (HDACs), as well as class I PI3K enzymes. Specifically, CUDC-907 is designed to inhibit HDACs 1, 2, 3, 6, and 10 and PI3K-alpha, delta, and beta isoforms.

Between Jan 23, 2013, and July 27, 2015, the phase 1 trial of CUDC-907 enrolled 44 patients who were refractory to or had relapsed after 2 or more previous regimens. The patients’ median age was 63 (range, 22-83), and they had received a median of 5 prior treatments (range, 2-10).

Four patients had MM, 12 had HL, and 12 had DLBCL. The remaining 16 patients had other types of lymphoma, including lymphoplasmacytic lymphoma (n=3), small lymphocytic lymphoma (n=3), mantle cell lymphoma (n=3), follicular lymphoma (n=2), T-cell lymphoma (n=2), marginal zone lymphoma (n=1), Burkitt lymphoma (n=1), and gray zone lymphoma (n=1).

Treatment

CUDC-907 was given in a standard 3 + 3 dose-escalation design at 4 different dosing schedules—once daily, twice weekly, 3 times weekly, and daily for 5 days followed by a 2-day break (5/2)—in 21-day cycles.

Patients continued to receive CUDC-907 until disease progression or other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose.

Ten patients were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to 3-times-weekly (MTD 150 mg), and 7 to the 5/2 dosing schedule (MTD 60 mg).

Safety

Four dose-limiting toxicities (DLTs) occurred in 3 of 40 DLT-evaluable patients. The DLTs were diarrhea and hyperglycemia in 1 patient on 60 mg once daily, hyperglycemia in 1 patient on 150 mg twice weekly, and diarrhea in 1 patient on 150 mg 3 times weekly. There were no DLTs in patients on the 5/2 schedule.

The incidence of grade 3 or higher adverse events (AEs) was 43% (19/44). The most common of these AEs were thrombocytopenia (20%, n=9), neutropenia (7%, n=3), and hyperglycemia (7%, n=3).

Twenty-five percent of patients (11/44) had serious AEs. Three of these events were considered treatment-related. They were epistaxis and the DLTs of diarrhea and hyperglycemia.

AEs led to dose reductions in 6 patients (14%) and treatment discontinuation in 7 patients (16%).

Efficacy

Thirty-seven patients were evaluable for response, and 5 of these patients responded (14%). All responses—2 complete and 3 partial responses—occurred in patients with DLBCL.

Twenty-one of the response-evaluable patients (57%) had stable disease. This included 1 patient with DLBCL, 2 with MM, 8 with HL, and 10 with the “other” types of lymphoma.

The remaining 11 patients progressed (30%)—3 with DLBCL, 2 with MM, 2 with HL, and 4 with other lymphomas.

Thirty-seven patients (84%) discontinued CUDC-907 because of progressive disease or clinical signs of progressive disease at the data cutoff.

Based on the clinical activity of CUDC-907 in patients with relapsed/refractory DLBCL, particularly those with MYC alterations, Curis has initiated a phase 2 trial of the drug in these patients. The recommended phase 2 dose is 60 mg on the 5/2 dosing schedule.

 

 

Micrograph showing DLBCL

 

The small-molecule inhibitor CUDC-907 can provide disease control in patients with relapsed or refractory lymphoma and multiple myeloma (MM), according to researchers.

In a phase 1 trial, CUDC-907 produced responses in a small number of patients with diffuse large B-cell lymphoma (DLBCL).

And more than half of patients had stable disease while on CUDC-907, including those with MM, DLBCL, Hodgkin lymphoma (HL), and other lymphomas.

However, a majority of patients in this trial—84%—discontinued treatment due to confirmed progressive disease or signs of progression.

These results were published in The Lancet. The trial was sponsored by Curis, Inc., the company developing CUDC-907, and the Leukemia and Lymphoma Society.

“The data from the phase 1 monotherapy trial for CUDC-907, especially in heavily pretreated patients with relapsed/refractory DLBCL are very encouraging, and we look forward to data emerging from the current phase 2 trial in patients with MYC-altered DLBCL,” said study author Anas Younes, MD, of the Memorial Sloan Kettering Cancer Center in New York, New York.

CUDC-907 is an oral, dual inhibitor of class I and II histone deacetylases (HDACs), as well as class I PI3K enzymes. Specifically, CUDC-907 is designed to inhibit HDACs 1, 2, 3, 6, and 10 and PI3K-alpha, delta, and beta isoforms.

Between Jan 23, 2013, and July 27, 2015, the phase 1 trial of CUDC-907 enrolled 44 patients who were refractory to or had relapsed after 2 or more previous regimens. The patients’ median age was 63 (range, 22-83), and they had received a median of 5 prior treatments (range, 2-10).

Four patients had MM, 12 had HL, and 12 had DLBCL. The remaining 16 patients had other types of lymphoma, including lymphoplasmacytic lymphoma (n=3), small lymphocytic lymphoma (n=3), mantle cell lymphoma (n=3), follicular lymphoma (n=2), T-cell lymphoma (n=2), marginal zone lymphoma (n=1), Burkitt lymphoma (n=1), and gray zone lymphoma (n=1).

Treatment

CUDC-907 was given in a standard 3 + 3 dose-escalation design at 4 different dosing schedules—once daily, twice weekly, 3 times weekly, and daily for 5 days followed by a 2-day break (5/2)—in 21-day cycles.

Patients continued to receive CUDC-907 until disease progression or other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose.

Ten patients were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to 3-times-weekly (MTD 150 mg), and 7 to the 5/2 dosing schedule (MTD 60 mg).

Safety

Four dose-limiting toxicities (DLTs) occurred in 3 of 40 DLT-evaluable patients. The DLTs were diarrhea and hyperglycemia in 1 patient on 60 mg once daily, hyperglycemia in 1 patient on 150 mg twice weekly, and diarrhea in 1 patient on 150 mg 3 times weekly. There were no DLTs in patients on the 5/2 schedule.

The incidence of grade 3 or higher adverse events (AEs) was 43% (19/44). The most common of these AEs were thrombocytopenia (20%, n=9), neutropenia (7%, n=3), and hyperglycemia (7%, n=3).

Twenty-five percent of patients (11/44) had serious AEs. Three of these events were considered treatment-related. They were epistaxis and the DLTs of diarrhea and hyperglycemia.

AEs led to dose reductions in 6 patients (14%) and treatment discontinuation in 7 patients (16%).

Efficacy

Thirty-seven patients were evaluable for response, and 5 of these patients responded (14%). All responses—2 complete and 3 partial responses—occurred in patients with DLBCL.

Twenty-one of the response-evaluable patients (57%) had stable disease. This included 1 patient with DLBCL, 2 with MM, 8 with HL, and 10 with the “other” types of lymphoma.

The remaining 11 patients progressed (30%)—3 with DLBCL, 2 with MM, 2 with HL, and 4 with other lymphomas.

Thirty-seven patients (84%) discontinued CUDC-907 because of progressive disease or clinical signs of progressive disease at the data cutoff.

Based on the clinical activity of CUDC-907 in patients with relapsed/refractory DLBCL, particularly those with MYC alterations, Curis has initiated a phase 2 trial of the drug in these patients. The recommended phase 2 dose is 60 mg on the 5/2 dosing schedule.

 

 

Micrograph showing DLBCL

 

The small-molecule inhibitor CUDC-907 can provide disease control in patients with relapsed or refractory lymphoma and multiple myeloma (MM), according to researchers.

In a phase 1 trial, CUDC-907 produced responses in a small number of patients with diffuse large B-cell lymphoma (DLBCL).

And more than half of patients had stable disease while on CUDC-907, including those with MM, DLBCL, Hodgkin lymphoma (HL), and other lymphomas.

However, a majority of patients in this trial—84%—discontinued treatment due to confirmed progressive disease or signs of progression.

These results were published in The Lancet. The trial was sponsored by Curis, Inc., the company developing CUDC-907, and the Leukemia and Lymphoma Society.

“The data from the phase 1 monotherapy trial for CUDC-907, especially in heavily pretreated patients with relapsed/refractory DLBCL are very encouraging, and we look forward to data emerging from the current phase 2 trial in patients with MYC-altered DLBCL,” said study author Anas Younes, MD, of the Memorial Sloan Kettering Cancer Center in New York, New York.

CUDC-907 is an oral, dual inhibitor of class I and II histone deacetylases (HDACs), as well as class I PI3K enzymes. Specifically, CUDC-907 is designed to inhibit HDACs 1, 2, 3, 6, and 10 and PI3K-alpha, delta, and beta isoforms.

Between Jan 23, 2013, and July 27, 2015, the phase 1 trial of CUDC-907 enrolled 44 patients who were refractory to or had relapsed after 2 or more previous regimens. The patients’ median age was 63 (range, 22-83), and they had received a median of 5 prior treatments (range, 2-10).

Four patients had MM, 12 had HL, and 12 had DLBCL. The remaining 16 patients had other types of lymphoma, including lymphoplasmacytic lymphoma (n=3), small lymphocytic lymphoma (n=3), mantle cell lymphoma (n=3), follicular lymphoma (n=2), T-cell lymphoma (n=2), marginal zone lymphoma (n=1), Burkitt lymphoma (n=1), and gray zone lymphoma (n=1).

Treatment

CUDC-907 was given in a standard 3 + 3 dose-escalation design at 4 different dosing schedules—once daily, twice weekly, 3 times weekly, and daily for 5 days followed by a 2-day break (5/2)—in 21-day cycles.

Patients continued to receive CUDC-907 until disease progression or other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose.

Ten patients were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to 3-times-weekly (MTD 150 mg), and 7 to the 5/2 dosing schedule (MTD 60 mg).

Safety

Four dose-limiting toxicities (DLTs) occurred in 3 of 40 DLT-evaluable patients. The DLTs were diarrhea and hyperglycemia in 1 patient on 60 mg once daily, hyperglycemia in 1 patient on 150 mg twice weekly, and diarrhea in 1 patient on 150 mg 3 times weekly. There were no DLTs in patients on the 5/2 schedule.

The incidence of grade 3 or higher adverse events (AEs) was 43% (19/44). The most common of these AEs were thrombocytopenia (20%, n=9), neutropenia (7%, n=3), and hyperglycemia (7%, n=3).

Twenty-five percent of patients (11/44) had serious AEs. Three of these events were considered treatment-related. They were epistaxis and the DLTs of diarrhea and hyperglycemia.

AEs led to dose reductions in 6 patients (14%) and treatment discontinuation in 7 patients (16%).

Efficacy

Thirty-seven patients were evaluable for response, and 5 of these patients responded (14%). All responses—2 complete and 3 partial responses—occurred in patients with DLBCL.

Twenty-one of the response-evaluable patients (57%) had stable disease. This included 1 patient with DLBCL, 2 with MM, 8 with HL, and 10 with the “other” types of lymphoma.

The remaining 11 patients progressed (30%)—3 with DLBCL, 2 with MM, 2 with HL, and 4 with other lymphomas.

Thirty-seven patients (84%) discontinued CUDC-907 because of progressive disease or clinical signs of progressive disease at the data cutoff.

Based on the clinical activity of CUDC-907 in patients with relapsed/refractory DLBCL, particularly those with MYC alterations, Curis has initiated a phase 2 trial of the drug in these patients. The recommended phase 2 dose is 60 mg on the 5/2 dosing schedule.