Amy Karon

SAN DIEGO – Adding bortezomib (B) to melphalan and dexamethasone (MDex) increased the frequency and depth of hematologic responses in a phase III trial of patients with previously untreated immunoglobulin light-chain (AL) amyloidosis.

Rates of hematologic response after three treatment cycles were 79% for BMDex and 52% for MDex (P = .002), Efstathios Kastritis, MD, said at the annual meeting of the American Society of Hematology. Very good partial responses accounted for most of this difference, with rates of 45% and 25%, respectively (P = .02). This first-in-kind trial establishes BMDex “as a novel standard of care in AL amyloidosis,” Dr. Kastritis concluded.

MDex is a standard regimen in intermediate-risk AL amyloidosis, while single-agent therapy with bortezomib yielded a median overall survival time of more than 5 years in one study, noted Dr. Kastritis of the University of Athens. In another matched case-control study, BMDex outperformed MDex based on overall response (69% vs. 51%; P = .01) and complete response (42% vs. 19%; P = .002).

Therefore, Dr. Kastritis and his associates in Europe and Australia randomly assigned 110 patients with newly diagnosed AL amyloidosis to receive either MDex (0.22 mg/kg melphalan plus 40 mg dexamethasone daily for 4 consecutive days every 28 days) or BMDex (MDex plus 1.3 mg/m² bortezomib on days 1, 4, 8, and 11 during cycles one and two, and on days 1, 8, 15, and 22 during subsequent cycles). Treatment continued through nine cycles of MDex or eight cycles of BMDex, or through cycle six if patients had either a complete response or a partial response plus an organ response. Patients stopped treatment after three cycles if they did not have at least a partial response.

After a median of five treatment cycles, BMDex and MDex led to similar rates of complete response (23% vs. 20%), partial response (19% and 17%), cardiac response (38% vs. 29%), and renal response (44% vs. 44%). Twenty-eight patients died, with no significant difference in overall survival between treatment arms. However, overall survival did favor BMDex (P = .03) among the 77 patients who were in cardiac stage II. Also, median time to second-line therapy was not reached for BMDex but was only 12 months with MDex (P less than .001).

The BMDex regimen was associated with higher rates of peripheral neuropathy (19% vs. 4% for MDex; P less than .001). Furthermore, three patients (1%) developed severe peripheral neuropathy on BMDex, while none did so on MDex. Grade 3 or higher adverse events were more common with BMDex than with MDex, but the difference did not reach statistical significance (52% vs. 40%; P = .13). There were four cardiac deaths in the first 100 days of the trial, three in the BMDex arm and one in the MDex arm (P = .31).

The European Myeloma Network sponsored the trial. Dr. Kastritis disclosed ties to Genesis, Takeda, Janssen, and Amgen.

SAN DIEGO – Adding bortezomib (B) to melphalan and dexamethasone (MDex) increased the frequency and depth of hematologic responses in a phase III trial of patients with previously untreated immunoglobulin light-chain (AL) amyloidosis.

Rates of hematologic response after three treatment cycles were 79% for BMDex and 52% for MDex (P = .002), Efstathios Kastritis, MD, said at the annual meeting of the American Society of Hematology. Very good partial responses accounted for most of this difference, with rates of 45% and 25%, respectively (P = .02). This first-in-kind trial establishes BMDex “as a novel standard of care in AL amyloidosis,” Dr. Kastritis concluded.

MDex is a standard regimen in intermediate-risk AL amyloidosis, while single-agent therapy with bortezomib yielded a median overall survival time of more than 5 years in one study, noted Dr. Kastritis of the University of Athens. In another matched case-control study, BMDex outperformed MDex based on overall response (69% vs. 51%; P = .01) and complete response (42% vs. 19%; P = .002).

Therefore, Dr. Kastritis and his associates in Europe and Australia randomly assigned 110 patients with newly diagnosed AL amyloidosis to receive either MDex (0.22 mg/kg melphalan plus 40 mg dexamethasone daily for 4 consecutive days every 28 days) or BMDex (MDex plus 1.3 mg/m² bortezomib on days 1, 4, 8, and 11 during cycles one and two, and on days 1, 8, 15, and 22 during subsequent cycles). Treatment continued through nine cycles of MDex or eight cycles of BMDex, or through cycle six if patients had either a complete response or a partial response plus an organ response. Patients stopped treatment after three cycles if they did not have at least a partial response.

After a median of five treatment cycles, BMDex and MDex led to similar rates of complete response (23% vs. 20%), partial response (19% and 17%), cardiac response (38% vs. 29%), and renal response (44% vs. 44%). Twenty-eight patients died, with no significant difference in overall survival between treatment arms. However, overall survival did favor BMDex (P = .03) among the 77 patients who were in cardiac stage II. Also, median time to second-line therapy was not reached for BMDex but was only 12 months with MDex (P less than .001).

The BMDex regimen was associated with higher rates of peripheral neuropathy (19% vs. 4% for MDex; P less than .001). Furthermore, three patients (1%) developed severe peripheral neuropathy on BMDex, while none did so on MDex. Grade 3 or higher adverse events were more common with BMDex than with MDex, but the difference did not reach statistical significance (52% vs. 40%; P = .13). There were four cardiac deaths in the first 100 days of the trial, three in the BMDex arm and one in the MDex arm (P = .31).

The European Myeloma Network sponsored the trial. Dr. Kastritis disclosed ties to Genesis, Takeda, Janssen, and Amgen.

SAN DIEGO – Adding bortezomib (B) to melphalan and dexamethasone (MDex) increased the frequency and depth of hematologic responses in a phase III trial of patients with previously untreated immunoglobulin light-chain (AL) amyloidosis.

Rates of hematologic response after three treatment cycles were 79% for BMDex and 52% for MDex (P = .002), Efstathios Kastritis, MD, said at the annual meeting of the American Society of Hematology. Very good partial responses accounted for most of this difference, with rates of 45% and 25%, respectively (P = .02). This first-in-kind trial establishes BMDex “as a novel standard of care in AL amyloidosis,” Dr. Kastritis concluded.

MDex is a standard regimen in intermediate-risk AL amyloidosis, while single-agent therapy with bortezomib yielded a median overall survival time of more than 5 years in one study, noted Dr. Kastritis of the University of Athens. In another matched case-control study, BMDex outperformed MDex based on overall response (69% vs. 51%; P = .01) and complete response (42% vs. 19%; P = .002).

Therefore, Dr. Kastritis and his associates in Europe and Australia randomly assigned 110 patients with newly diagnosed AL amyloidosis to receive either MDex (0.22 mg/kg melphalan plus 40 mg dexamethasone daily for 4 consecutive days every 28 days) or BMDex (MDex plus 1.3 mg/m² bortezomib on days 1, 4, 8, and 11 during cycles one and two, and on days 1, 8, 15, and 22 during subsequent cycles). Treatment continued through nine cycles of MDex or eight cycles of BMDex, or through cycle six if patients had either a complete response or a partial response plus an organ response. Patients stopped treatment after three cycles if they did not have at least a partial response.

After a median of five treatment cycles, BMDex and MDex led to similar rates of complete response (23% vs. 20%), partial response (19% and 17%), cardiac response (38% vs. 29%), and renal response (44% vs. 44%). Twenty-eight patients died, with no significant difference in overall survival between treatment arms. However, overall survival did favor BMDex (P = .03) among the 77 patients who were in cardiac stage II. Also, median time to second-line therapy was not reached for BMDex but was only 12 months with MDex (P less than .001).

The BMDex regimen was associated with higher rates of peripheral neuropathy (19% vs. 4% for MDex; P less than .001). Furthermore, three patients (1%) developed severe peripheral neuropathy on BMDex, while none did so on MDex. Grade 3 or higher adverse events were more common with BMDex than with MDex, but the difference did not reach statistical significance (52% vs. 40%; P = .13). There were four cardiac deaths in the first 100 days of the trial, three in the BMDex arm and one in the MDex arm (P = .31).

The European Myeloma Network sponsored the trial. Dr. Kastritis disclosed ties to Genesis, Takeda, Janssen, and Amgen.

SAN DIEGO – Having less than three focal lesions on FDG-PET/CT (fluorodeoxyglucose positron emission tomography integrated with computed tomography) when beginning lenalidomide maintenance therapy predicted significantly higher rates of progression-free and overall survival among patients with newly diagnosed multiple myeloma.

Survival in this prospective study of 102 patients also correlated with FDG uptake that did not exceed the level of the liver (Deauville score less than 3), reported Elena Zamagni, MD, PhD, of Bologna (Italy) University. The findings highlight FDG-PET/CT as “a powerful prognostic marker for survival, both in terms of number and score of focal lesions,” she said during an oral presentation at the annual meeting of the American Society of Hematology.

Although FDG-PET/CT is “well recognized” for staging and evaluating prognosis in multiple myeloma, a “major inconsistency in methodology between studies” inspired the current analysis, Dr. Zamagni said. “Different groups have used different interpretation criteria and arbitrary cutoffs with very variable results, especially in terms of posttreatment and borderline cases,” she noted.

Therefore, researchers from eight participating centers evaluated FDG-PET/CT scans from 103 patients with newly diagnosed multiple myeloma who were part of the randomized phase III EMN02 trial. Scans were performed at diagnosis, at the start of induction therapy, and just before patients started maintenance therapy with lenalidomide. Five nuclear medicine experts reviewed the scans in a blinded manner.

About 34% of patients had positive focal lesions on FDG-PET/CT at the start of maintenance, Dr. Zamagni said. After a median follow-up of 2 years, rates of progression-free survival were 84% in those with fewer than three focal lesions and 47% in those with three or more lesions (hazard ratio, 3.5; P = .01). Rates of overall survival followed the same trend at 98% and 68%, respectively (HR, 13.6; P = .0002).

Likewise, among patients whose FDG uptake did not exceed that of the liver, 2-year rates of progression-free and overall survival were 87% and 100%, compared with 69% and 45% in patients with new focal lesions or slightly, moderately, or markedly greater FDG uptake than the liver (Deauville scores of 4 and 5; P less than .001 for each comparison).

Normalization of FDG-PET/CT after induction also predicted improved survival, Dr. Zamagni said. Two-year progression-free survival rates were 85% among patients who had become PET-negative by the time they began maintenance, but were only 66% among patients who remained PET-positive (HR, 1.5; P less than .01). Rates of overall survival at 2 years were 98% among PET-negative patients and 87% among PET-positive patients (HR, 1.6; P = .03).

The study also confirmed the value of performing FDG-PET/CT at de novo myeloma diagnosis. Strikingly, only 20% of patients with baseline FDG-PET/CT evidence of extramedullary disease at this time point were alive and progression free 2 years later, compared with 81% of those without extramedullary disease (HR, 5.0; P = .001). Once again, the same trend emerged for Deauville scores – 99% of patients with scores of 3 or lower at diagnosis were alive 2 years later, compared with 83% of those who scored 4 or 5 (HR, 5.6; P = .03).

The EMN02 trial included 714 patients with newly diagnosed multiple myeloma who underwent induction with bortezomib-cyclophosphamide-dexamethasone (VCD), followed by either standard-dose intensification therapy with bortezomib-melphalan-prednisone (VMP) or high-dose intensification therapy with melphalan followed by single or double autologous stem cell transplantation. After that, patients either underwent consolidation therapy followed by lenalidomide maintenance therapy or proceeded directly to maintenance. Among the study subgroup of 103 patients, median age was 58 years, 25% of patients had high-risk cytogenetics, and 15% were ISS stage III.

“FDG-PET/CT is by now the preferred imaging technique for evaluating and monitoring response to therapy,” Dr. Zamagni concluded. She and her associates will use data from four other trials to further validate prognostic criteria and more precisely define cutoff points, she said.

Fondazione del Monte di Bologna e Ravenna partially supported the study. Dr. Zamagni had no relevant financial conflicts of interest.

SAN DIEGO – Having less than three focal lesions on FDG-PET/CT (fluorodeoxyglucose positron emission tomography integrated with computed tomography) when beginning lenalidomide maintenance therapy predicted significantly higher rates of progression-free and overall survival among patients with newly diagnosed multiple myeloma.

Survival in this prospective study of 102 patients also correlated with FDG uptake that did not exceed the level of the liver (Deauville score less than 3), reported Elena Zamagni, MD, PhD, of Bologna (Italy) University. The findings highlight FDG-PET/CT as “a powerful prognostic marker for survival, both in terms of number and score of focal lesions,” she said during an oral presentation at the annual meeting of the American Society of Hematology.

Although FDG-PET/CT is “well recognized” for staging and evaluating prognosis in multiple myeloma, a “major inconsistency in methodology between studies” inspired the current analysis, Dr. Zamagni said. “Different groups have used different interpretation criteria and arbitrary cutoffs with very variable results, especially in terms of posttreatment and borderline cases,” she noted.

Therefore, researchers from eight participating centers evaluated FDG-PET/CT scans from 103 patients with newly diagnosed multiple myeloma who were part of the randomized phase III EMN02 trial. Scans were performed at diagnosis, at the start of induction therapy, and just before patients started maintenance therapy with lenalidomide. Five nuclear medicine experts reviewed the scans in a blinded manner.

About 34% of patients had positive focal lesions on FDG-PET/CT at the start of maintenance, Dr. Zamagni said. After a median follow-up of 2 years, rates of progression-free survival were 84% in those with fewer than three focal lesions and 47% in those with three or more lesions (hazard ratio, 3.5; P = .01). Rates of overall survival followed the same trend at 98% and 68%, respectively (HR, 13.6; P = .0002).

Likewise, among patients whose FDG uptake did not exceed that of the liver, 2-year rates of progression-free and overall survival were 87% and 100%, compared with 69% and 45% in patients with new focal lesions or slightly, moderately, or markedly greater FDG uptake than the liver (Deauville scores of 4 and 5; P less than .001 for each comparison).

Normalization of FDG-PET/CT after induction also predicted improved survival, Dr. Zamagni said. Two-year progression-free survival rates were 85% among patients who had become PET-negative by the time they began maintenance, but were only 66% among patients who remained PET-positive (HR, 1.5; P less than .01). Rates of overall survival at 2 years were 98% among PET-negative patients and 87% among PET-positive patients (HR, 1.6; P = .03).

The study also confirmed the value of performing FDG-PET/CT at de novo myeloma diagnosis. Strikingly, only 20% of patients with baseline FDG-PET/CT evidence of extramedullary disease at this time point were alive and progression free 2 years later, compared with 81% of those without extramedullary disease (HR, 5.0; P = .001). Once again, the same trend emerged for Deauville scores – 99% of patients with scores of 3 or lower at diagnosis were alive 2 years later, compared with 83% of those who scored 4 or 5 (HR, 5.6; P = .03).

The EMN02 trial included 714 patients with newly diagnosed multiple myeloma who underwent induction with bortezomib-cyclophosphamide-dexamethasone (VCD), followed by either standard-dose intensification therapy with bortezomib-melphalan-prednisone (VMP) or high-dose intensification therapy with melphalan followed by single or double autologous stem cell transplantation. After that, patients either underwent consolidation therapy followed by lenalidomide maintenance therapy or proceeded directly to maintenance. Among the study subgroup of 103 patients, median age was 58 years, 25% of patients had high-risk cytogenetics, and 15% were ISS stage III.

“FDG-PET/CT is by now the preferred imaging technique for evaluating and monitoring response to therapy,” Dr. Zamagni concluded. She and her associates will use data from four other trials to further validate prognostic criteria and more precisely define cutoff points, she said.

Fondazione del Monte di Bologna e Ravenna partially supported the study. Dr. Zamagni had no relevant financial conflicts of interest.

SAN DIEGO – Having less than three focal lesions on FDG-PET/CT (fluorodeoxyglucose positron emission tomography integrated with computed tomography) when beginning lenalidomide maintenance therapy predicted significantly higher rates of progression-free and overall survival among patients with newly diagnosed multiple myeloma.

Survival in this prospective study of 102 patients also correlated with FDG uptake that did not exceed the level of the liver (Deauville score less than 3), reported Elena Zamagni, MD, PhD, of Bologna (Italy) University. The findings highlight FDG-PET/CT as “a powerful prognostic marker for survival, both in terms of number and score of focal lesions,” she said during an oral presentation at the annual meeting of the American Society of Hematology.

Although FDG-PET/CT is “well recognized” for staging and evaluating prognosis in multiple myeloma, a “major inconsistency in methodology between studies” inspired the current analysis, Dr. Zamagni said. “Different groups have used different interpretation criteria and arbitrary cutoffs with very variable results, especially in terms of posttreatment and borderline cases,” she noted.

Therefore, researchers from eight participating centers evaluated FDG-PET/CT scans from 103 patients with newly diagnosed multiple myeloma who were part of the randomized phase III EMN02 trial. Scans were performed at diagnosis, at the start of induction therapy, and just before patients started maintenance therapy with lenalidomide. Five nuclear medicine experts reviewed the scans in a blinded manner.

About 34% of patients had positive focal lesions on FDG-PET/CT at the start of maintenance, Dr. Zamagni said. After a median follow-up of 2 years, rates of progression-free survival were 84% in those with fewer than three focal lesions and 47% in those with three or more lesions (hazard ratio, 3.5; P = .01). Rates of overall survival followed the same trend at 98% and 68%, respectively (HR, 13.6; P = .0002).

Likewise, among patients whose FDG uptake did not exceed that of the liver, 2-year rates of progression-free and overall survival were 87% and 100%, compared with 69% and 45% in patients with new focal lesions or slightly, moderately, or markedly greater FDG uptake than the liver (Deauville scores of 4 and 5; P less than .001 for each comparison).

Normalization of FDG-PET/CT after induction also predicted improved survival, Dr. Zamagni said. Two-year progression-free survival rates were 85% among patients who had become PET-negative by the time they began maintenance, but were only 66% among patients who remained PET-positive (HR, 1.5; P less than .01). Rates of overall survival at 2 years were 98% among PET-negative patients and 87% among PET-positive patients (HR, 1.6; P = .03).

The study also confirmed the value of performing FDG-PET/CT at de novo myeloma diagnosis. Strikingly, only 20% of patients with baseline FDG-PET/CT evidence of extramedullary disease at this time point were alive and progression free 2 years later, compared with 81% of those without extramedullary disease (HR, 5.0; P = .001). Once again, the same trend emerged for Deauville scores – 99% of patients with scores of 3 or lower at diagnosis were alive 2 years later, compared with 83% of those who scored 4 or 5 (HR, 5.6; P = .03).

The EMN02 trial included 714 patients with newly diagnosed multiple myeloma who underwent induction with bortezomib-cyclophosphamide-dexamethasone (VCD), followed by either standard-dose intensification therapy with bortezomib-melphalan-prednisone (VMP) or high-dose intensification therapy with melphalan followed by single or double autologous stem cell transplantation. After that, patients either underwent consolidation therapy followed by lenalidomide maintenance therapy or proceeded directly to maintenance. Among the study subgroup of 103 patients, median age was 58 years, 25% of patients had high-risk cytogenetics, and 15% were ISS stage III.

“FDG-PET/CT is by now the preferred imaging technique for evaluating and monitoring response to therapy,” Dr. Zamagni concluded. She and her associates will use data from four other trials to further validate prognostic criteria and more precisely define cutoff points, she said.

Fondazione del Monte di Bologna e Ravenna partially supported the study. Dr. Zamagni had no relevant financial conflicts of interest.

SAN DIEGO – A chemotherapy-free induction regimen of ibrutinib and rituximab was well tolerated and achieved an overall response rate of 100% among patients with newly diagnosed mantle cell lymphoma (MCL), according to results of a small single-center phase II trial.

A total of 72% of patients had complete responses to induction, while 28% had partial responses, and 100% had complete responses to consolidation, reported Michael Wang, MD, at the annual meeting of the American Society of Hematology. The findings highlight a “window of opportunity” to effectively treat de novo MCL in young, fit patients while potentially sparing them from repeated cycles of intensive chemoimmunotherapy, the investigators noted.

Established treatments for MCL include eight cycles of rituximab–hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with rituximab–methotrexate–Ara-C (cytarabine). Median overall survival with this regimen exceeds 10 years, but during that decade, more than 6% of patients will develop myeloid neoplasms related to treatment, noted Dr. Wang of the University of Texas MD Anderson Cancer Center in Houston.

For the study, patients up to 65 years old with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib (560 mg), plus rituximab (375 mg/m²) administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD, alternating every 28 days with rituximab plus high-dose methotrexate–Ara-C. Complete responders to induction received four cycles of chemoimmunotherapy, while progressors and partial responders received chemoimmunotherapy for two cycles beyond the point of complete remission.

Among 36 evaluable patients, 28% had a partial response and the rest had complete responses to induction. Moreover, all 19 patients who completed consolidation had a complete response. During induction, the most common toxicities were fatigue, diarrhea, rash, and myalgia, nearly all of which were mild or moderate in severity. During consolidation, two patients developed severe neutropenia, one patient developed severe febrile neutropenia, and one developed a severe increase in liver enzymes. There were no treatment-related deaths.

“The toxicity after intensive immune-chemotherapy in shortened cycles [is] much improved compared to historical controls, but longer follow-up is needed,” the researchers wrote. “This unprecedented efficacy and safety may provide a window of opportunity for less chemoimmunotherapy needed for consolidation.”

Dr. Wang disclosed ties to Janssen, Onyx, BeiGene, Kite Pharma, Asana Biosciences, Juno Therapeutics, Acerta Pharma, and Celgene.

SAN DIEGO – A chemotherapy-free induction regimen of ibrutinib and rituximab was well tolerated and achieved an overall response rate of 100% among patients with newly diagnosed mantle cell lymphoma (MCL), according to results of a small single-center phase II trial.

A total of 72% of patients had complete responses to induction, while 28% had partial responses, and 100% had complete responses to consolidation, reported Michael Wang, MD, at the annual meeting of the American Society of Hematology. The findings highlight a “window of opportunity” to effectively treat de novo MCL in young, fit patients while potentially sparing them from repeated cycles of intensive chemoimmunotherapy, the investigators noted.

Established treatments for MCL include eight cycles of rituximab–hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with rituximab–methotrexate–Ara-C (cytarabine). Median overall survival with this regimen exceeds 10 years, but during that decade, more than 6% of patients will develop myeloid neoplasms related to treatment, noted Dr. Wang of the University of Texas MD Anderson Cancer Center in Houston.

For the study, patients up to 65 years old with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib (560 mg), plus rituximab (375 mg/m²) administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD, alternating every 28 days with rituximab plus high-dose methotrexate–Ara-C. Complete responders to induction received four cycles of chemoimmunotherapy, while progressors and partial responders received chemoimmunotherapy for two cycles beyond the point of complete remission.

Among 36 evaluable patients, 28% had a partial response and the rest had complete responses to induction. Moreover, all 19 patients who completed consolidation had a complete response. During induction, the most common toxicities were fatigue, diarrhea, rash, and myalgia, nearly all of which were mild or moderate in severity. During consolidation, two patients developed severe neutropenia, one patient developed severe febrile neutropenia, and one developed a severe increase in liver enzymes. There were no treatment-related deaths.

“The toxicity after intensive immune-chemotherapy in shortened cycles [is] much improved compared to historical controls, but longer follow-up is needed,” the researchers wrote. “This unprecedented efficacy and safety may provide a window of opportunity for less chemoimmunotherapy needed for consolidation.”

Dr. Wang disclosed ties to Janssen, Onyx, BeiGene, Kite Pharma, Asana Biosciences, Juno Therapeutics, Acerta Pharma, and Celgene.

SAN DIEGO – A chemotherapy-free induction regimen of ibrutinib and rituximab was well tolerated and achieved an overall response rate of 100% among patients with newly diagnosed mantle cell lymphoma (MCL), according to results of a small single-center phase II trial.

A total of 72% of patients had complete responses to induction, while 28% had partial responses, and 100% had complete responses to consolidation, reported Michael Wang, MD, at the annual meeting of the American Society of Hematology. The findings highlight a “window of opportunity” to effectively treat de novo MCL in young, fit patients while potentially sparing them from repeated cycles of intensive chemoimmunotherapy, the investigators noted.

Established treatments for MCL include eight cycles of rituximab–hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with rituximab–methotrexate–Ara-C (cytarabine). Median overall survival with this regimen exceeds 10 years, but during that decade, more than 6% of patients will develop myeloid neoplasms related to treatment, noted Dr. Wang of the University of Texas MD Anderson Cancer Center in Houston.

For the study, patients up to 65 years old with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib (560 mg), plus rituximab (375 mg/m²) administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD, alternating every 28 days with rituximab plus high-dose methotrexate–Ara-C. Complete responders to induction received four cycles of chemoimmunotherapy, while progressors and partial responders received chemoimmunotherapy for two cycles beyond the point of complete remission.

Among 36 evaluable patients, 28% had a partial response and the rest had complete responses to induction. Moreover, all 19 patients who completed consolidation had a complete response. During induction, the most common toxicities were fatigue, diarrhea, rash, and myalgia, nearly all of which were mild or moderate in severity. During consolidation, two patients developed severe neutropenia, one patient developed severe febrile neutropenia, and one developed a severe increase in liver enzymes. There were no treatment-related deaths.

“The toxicity after intensive immune-chemotherapy in shortened cycles [is] much improved compared to historical controls, but longer follow-up is needed,” the researchers wrote. “This unprecedented efficacy and safety may provide a window of opportunity for less chemoimmunotherapy needed for consolidation.”

Dr. Wang disclosed ties to Janssen, Onyx, BeiGene, Kite Pharma, Asana Biosciences, Juno Therapeutics, Acerta Pharma, and Celgene.

In a global survey, 88% of respondents knew that unprotected sun exposure leads to skin cancer, but less than 60% “always” or “often” applied sunscreen to their faces, arms, and legs, researchers said.

Many respondents also reported ignoring whole categories of sun-protective behaviors – such as wearing long sleeves and seeking shade – and lacked knowledge about individual risk factors for skin cancer, such as skin type and size of moles, Sophie Seite, PhD, and her coauthors reported in the Journal of the European Academy of Dermatology and Venereology. These data suggest “that messaging needs to be specifically targeted for at-risk demographics (especially by age, gender, skin type, and country),” they added.

karenfoleyphotography/Thinkstock

In a global survey, 88% of respondents knew that unprotected sun exposure leads to skin cancer, but less than 60% “always” or “often” applied sunscreen to their faces, arms, and legs, researchers said.

Many respondents also reported ignoring whole categories of sun-protective behaviors – such as wearing long sleeves and seeking shade – and lacked knowledge about individual risk factors for skin cancer, such as skin type and size of moles, Sophie Seite, PhD, and her coauthors reported in the Journal of the European Academy of Dermatology and Venereology. These data suggest “that messaging needs to be specifically targeted for at-risk demographics (especially by age, gender, skin type, and country),” they added.

karenfoleyphotography/Thinkstock

In a global survey, 88% of respondents knew that unprotected sun exposure leads to skin cancer, but less than 60% “always” or “often” applied sunscreen to their faces, arms, and legs, researchers said.

Many respondents also reported ignoring whole categories of sun-protective behaviors – such as wearing long sleeves and seeking shade – and lacked knowledge about individual risk factors for skin cancer, such as skin type and size of moles, Sophie Seite, PhD, and her coauthors reported in the Journal of the European Academy of Dermatology and Venereology. These data suggest “that messaging needs to be specifically targeted for at-risk demographics (especially by age, gender, skin type, and country),” they added.

karenfoleyphotography/Thinkstock

SAN DIEGO – Patients with chronic lymphocytic leukemia at risk for early relapse were about 85% less likely to progress on lenalidomide maintenance therapy compared with placebo, based on an interim analysis of the randomized phase III CLLM1 study.

After a typical follow-up time of 17.5 months, median durations of progression-free survival were not reached with lenalidomide and were 13 months with placebo, for a hazard ratio of 0.15 (95% confidence interval, 0.06-0.35). These results were “statistically significant, robust, and reliable in favor of lenalidomide,” Anna Fink, MD, said at the 2016 meeting of the American Society of Hematology. Several patients in the lenalidomide arm also converted to minimal residual disease (MRD) negativity, added Dr. Fink of University Hospital Cologne (Germany).

The study included patients whose CLL responded at least partially to front-line chemoimmunotherapy, but who were at high risk of progression – minimal residual disease levels were at least 10^–2, or were between 10^–4 and 10^–2 in patients who also had an unmutated IGHV gene status or del(17p) or TP53 mutations at baseline. Among 89 patients who met these criteria, 60 received lenalidomide maintenance and 20 received placebo.

The initial lenalidomide cycle consisted of 5 mg daily for 28 days. To achieve MRD negativity, clinicians increased this dose during subsequent cycles to a maximum of 15 mg daily for patients who were MRD negative after cycle 12, 20 mg for patients who were MRD negative after cycle 18, and 25 mg for patients who remained MRD positive. Median age was 64 years, more than 80% of patients were male, and the median cumulative illness rating was relatively low at 2, ranging between 0 and 8.

A total of 37% of patients had a high MRD level and 63% had an intermediate level. For both cohorts, lenalidomide maintenance significantly prolonged progression-free survival, compared with placebo, with hazard ratios of 0.17 and 0.13, respectively. Patients received a median of 11 and up to 40 cycles of lenalidomide, but a median of only 8 cycles of placebo.

In all, 43% of lenalidomide patients and 72% of placebo patients stopped maintenance. Nearly a third of those who discontinued lenalidomide did so because of adverse events, but 45% of patients who stopped placebo did so because of progressive disease, Dr. Fink said. Lenalidomide was associated with more neutropenia, gastrointestinal disorders, nervous system disorders, and respiratory and skin disorders than was placebo, but the events were usually mild to moderate in severity, she added.

The three deaths in this study yielded no treatment-based difference in rates of overall survival. Causes of death included acute lymphoblastic leukemia (lenalidomide arm), progressive multifocal leukoencephalopathy (placebo), and Richter’s syndrome (placebo). Venous thromboembolic events were uncommon because patients were given low-dose aspirin or anticoagulant therapy, Dr. Fink noted.

“Lenalidomide is a feasible and efficacious maintenance option for high-risk CLL after chemoimmunotherapy,” she concluded. The low duration of progression-free survival in the placebo group confirms the prognostic utility of assessing risk based on MRD, which might be useful in future studies, she added.

The German CLL Study Group sponsored the trial. Dr. Fink disclosed ties to Mundipharma, Roche, Celgene, and AbbVie.

SAN DIEGO – Patients with chronic lymphocytic leukemia at risk for early relapse were about 85% less likely to progress on lenalidomide maintenance therapy compared with placebo, based on an interim analysis of the randomized phase III CLLM1 study.

After a typical follow-up time of 17.5 months, median durations of progression-free survival were not reached with lenalidomide and were 13 months with placebo, for a hazard ratio of 0.15 (95% confidence interval, 0.06-0.35). These results were “statistically significant, robust, and reliable in favor of lenalidomide,” Anna Fink, MD, said at the 2016 meeting of the American Society of Hematology. Several patients in the lenalidomide arm also converted to minimal residual disease (MRD) negativity, added Dr. Fink of University Hospital Cologne (Germany).

The study included patients whose CLL responded at least partially to front-line chemoimmunotherapy, but who were at high risk of progression – minimal residual disease levels were at least 10^–2, or were between 10^–4 and 10^–2 in patients who also had an unmutated IGHV gene status or del(17p) or TP53 mutations at baseline. Among 89 patients who met these criteria, 60 received lenalidomide maintenance and 20 received placebo.

The initial lenalidomide cycle consisted of 5 mg daily for 28 days. To achieve MRD negativity, clinicians increased this dose during subsequent cycles to a maximum of 15 mg daily for patients who were MRD negative after cycle 12, 20 mg for patients who were MRD negative after cycle 18, and 25 mg for patients who remained MRD positive. Median age was 64 years, more than 80% of patients were male, and the median cumulative illness rating was relatively low at 2, ranging between 0 and 8.

A total of 37% of patients had a high MRD level and 63% had an intermediate level. For both cohorts, lenalidomide maintenance significantly prolonged progression-free survival, compared with placebo, with hazard ratios of 0.17 and 0.13, respectively. Patients received a median of 11 and up to 40 cycles of lenalidomide, but a median of only 8 cycles of placebo.

In all, 43% of lenalidomide patients and 72% of placebo patients stopped maintenance. Nearly a third of those who discontinued lenalidomide did so because of adverse events, but 45% of patients who stopped placebo did so because of progressive disease, Dr. Fink said. Lenalidomide was associated with more neutropenia, gastrointestinal disorders, nervous system disorders, and respiratory and skin disorders than was placebo, but the events were usually mild to moderate in severity, she added.

The three deaths in this study yielded no treatment-based difference in rates of overall survival. Causes of death included acute lymphoblastic leukemia (lenalidomide arm), progressive multifocal leukoencephalopathy (placebo), and Richter’s syndrome (placebo). Venous thromboembolic events were uncommon because patients were given low-dose aspirin or anticoagulant therapy, Dr. Fink noted.

“Lenalidomide is a feasible and efficacious maintenance option for high-risk CLL after chemoimmunotherapy,” she concluded. The low duration of progression-free survival in the placebo group confirms the prognostic utility of assessing risk based on MRD, which might be useful in future studies, she added.

The German CLL Study Group sponsored the trial. Dr. Fink disclosed ties to Mundipharma, Roche, Celgene, and AbbVie.

SAN DIEGO – Patients with chronic lymphocytic leukemia at risk for early relapse were about 85% less likely to progress on lenalidomide maintenance therapy compared with placebo, based on an interim analysis of the randomized phase III CLLM1 study.

After a typical follow-up time of 17.5 months, median durations of progression-free survival were not reached with lenalidomide and were 13 months with placebo, for a hazard ratio of 0.15 (95% confidence interval, 0.06-0.35). These results were “statistically significant, robust, and reliable in favor of lenalidomide,” Anna Fink, MD, said at the 2016 meeting of the American Society of Hematology. Several patients in the lenalidomide arm also converted to minimal residual disease (MRD) negativity, added Dr. Fink of University Hospital Cologne (Germany).

The study included patients whose CLL responded at least partially to front-line chemoimmunotherapy, but who were at high risk of progression – minimal residual disease levels were at least 10^–2, or were between 10^–4 and 10^–2 in patients who also had an unmutated IGHV gene status or del(17p) or TP53 mutations at baseline. Among 89 patients who met these criteria, 60 received lenalidomide maintenance and 20 received placebo.

The initial lenalidomide cycle consisted of 5 mg daily for 28 days. To achieve MRD negativity, clinicians increased this dose during subsequent cycles to a maximum of 15 mg daily for patients who were MRD negative after cycle 12, 20 mg for patients who were MRD negative after cycle 18, and 25 mg for patients who remained MRD positive. Median age was 64 years, more than 80% of patients were male, and the median cumulative illness rating was relatively low at 2, ranging between 0 and 8.

A total of 37% of patients had a high MRD level and 63% had an intermediate level. For both cohorts, lenalidomide maintenance significantly prolonged progression-free survival, compared with placebo, with hazard ratios of 0.17 and 0.13, respectively. Patients received a median of 11 and up to 40 cycles of lenalidomide, but a median of only 8 cycles of placebo.

In all, 43% of lenalidomide patients and 72% of placebo patients stopped maintenance. Nearly a third of those who discontinued lenalidomide did so because of adverse events, but 45% of patients who stopped placebo did so because of progressive disease, Dr. Fink said. Lenalidomide was associated with more neutropenia, gastrointestinal disorders, nervous system disorders, and respiratory and skin disorders than was placebo, but the events were usually mild to moderate in severity, she added.

The three deaths in this study yielded no treatment-based difference in rates of overall survival. Causes of death included acute lymphoblastic leukemia (lenalidomide arm), progressive multifocal leukoencephalopathy (placebo), and Richter’s syndrome (placebo). Venous thromboembolic events were uncommon because patients were given low-dose aspirin or anticoagulant therapy, Dr. Fink noted.

“Lenalidomide is a feasible and efficacious maintenance option for high-risk CLL after chemoimmunotherapy,” she concluded. The low duration of progression-free survival in the placebo group confirms the prognostic utility of assessing risk based on MRD, which might be useful in future studies, she added.

The German CLL Study Group sponsored the trial. Dr. Fink disclosed ties to Mundipharma, Roche, Celgene, and AbbVie.

SAN DIEGO – Rituximab can at least temporarily vanquish minimal residual disease (MRD) in mantle cell lymphoma (MCL) patients who relapse after induction therapy and autologous stem cell transplantation (ASCT), researchers reported at the annual meeting of the American Society of Hematology.

Of 58 patients whose MCL relapsed after induction therapy and ASCT, 82% converted back to an MRD-negative state after receiving 4 weekly doses of rituximab (375 mg/m²), Arne Kolstad, MD, PhD, and his associates. The data “strongly suggest that preemptive rituximab treatment delayed clinical relapse in MCL,” they wrote in their abstract. They recommended molecular and clinical monitoring after ASCT, not only “as an alternative to maintenance therapy for all MCL patients” but to identify MRD-positive candidates for clinical trials.

The study was an analysis of the Nordic Lymphoma Group phase II MCL2 and MCL3 trials (NTC 00514475), in which patients received six alternating cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) and R-Ara-C (rituximab-cytarabine). followed by high-dose ASCT. In MCL3, responders who fell short of complete remission also received intensification with yttium-90 ibritumomab tiuxetan (0.4 mCi/kg) 1 week before treatment with BEAM/C (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide). Patients were evaluated 2-3 months after completing ASCT, and then every 6 months for 5 years or until relapse. Survivors were followed for a median of 8.5 years, noted Dr. Kolstad, who is with Oslo University Hospital in Norway.

Among 183 patients who underwent polymerase chain reaction–based testing for markers of MRD, median time to molecular relapse was 55 months. However, the relapse-free survival curve did not plateau – patients in all risk groups continued to relapse 5-10 years after undergoing ASCT, the researchers said. “Hence, it is fair to consider MCL as a chronic incurable lymphoma entity, and novel approaches will be necessary to change the natural course of this disease,” they wrote.

After controlling for potential confounders, significant predictors of molecular relapse included high MCL international prognostic index at diagnosis (hazard ratio, 1.9; 95% confidence interval 1.4-2.7; P = .0001) and detection of MRD before patients underwent ASCT (HR, 2.5; 95% CI, 1.5-4.1; P = .0005). Minimal residual disease predicted clinical relapse and shorter survival (P less than .001 for both associations). In contrast, the 86 patients who remained in continuous molecular remission had a 76% chance of having at least a 10-year clinical remission, the investigators said.

Minimal residual disease was assessed by testing bone marrow and blood samples with combined standard nested and quantitative real-time polymerase chain reaction (PCR) for Bcl-1 or IgH rearrangement. They defined molecular relapse as conversion from a negative to a positive result on standard nested PCR, or, for patients who were MRD positive after ASCT, as a more than fivefold rise in real-time quantitative PCR levels in two consecutive bone marrow samples.

Oslo University sponsored the trials. Dr. Kolstad reported ties to Nordic Nanovector, Bayer Schering Pharma, Merck, and Roche.

SAN DIEGO – Rituximab can at least temporarily vanquish minimal residual disease (MRD) in mantle cell lymphoma (MCL) patients who relapse after induction therapy and autologous stem cell transplantation (ASCT), researchers reported at the annual meeting of the American Society of Hematology.

Of 58 patients whose MCL relapsed after induction therapy and ASCT, 82% converted back to an MRD-negative state after receiving 4 weekly doses of rituximab (375 mg/m²), Arne Kolstad, MD, PhD, and his associates. The data “strongly suggest that preemptive rituximab treatment delayed clinical relapse in MCL,” they wrote in their abstract. They recommended molecular and clinical monitoring after ASCT, not only “as an alternative to maintenance therapy for all MCL patients” but to identify MRD-positive candidates for clinical trials.

The study was an analysis of the Nordic Lymphoma Group phase II MCL2 and MCL3 trials (NTC 00514475), in which patients received six alternating cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) and R-Ara-C (rituximab-cytarabine). followed by high-dose ASCT. In MCL3, responders who fell short of complete remission also received intensification with yttium-90 ibritumomab tiuxetan (0.4 mCi/kg) 1 week before treatment with BEAM/C (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide). Patients were evaluated 2-3 months after completing ASCT, and then every 6 months for 5 years or until relapse. Survivors were followed for a median of 8.5 years, noted Dr. Kolstad, who is with Oslo University Hospital in Norway.

Among 183 patients who underwent polymerase chain reaction–based testing for markers of MRD, median time to molecular relapse was 55 months. However, the relapse-free survival curve did not plateau – patients in all risk groups continued to relapse 5-10 years after undergoing ASCT, the researchers said. “Hence, it is fair to consider MCL as a chronic incurable lymphoma entity, and novel approaches will be necessary to change the natural course of this disease,” they wrote.

After controlling for potential confounders, significant predictors of molecular relapse included high MCL international prognostic index at diagnosis (hazard ratio, 1.9; 95% confidence interval 1.4-2.7; P = .0001) and detection of MRD before patients underwent ASCT (HR, 2.5; 95% CI, 1.5-4.1; P = .0005). Minimal residual disease predicted clinical relapse and shorter survival (P less than .001 for both associations). In contrast, the 86 patients who remained in continuous molecular remission had a 76% chance of having at least a 10-year clinical remission, the investigators said.

Minimal residual disease was assessed by testing bone marrow and blood samples with combined standard nested and quantitative real-time polymerase chain reaction (PCR) for Bcl-1 or IgH rearrangement. They defined molecular relapse as conversion from a negative to a positive result on standard nested PCR, or, for patients who were MRD positive after ASCT, as a more than fivefold rise in real-time quantitative PCR levels in two consecutive bone marrow samples.

Oslo University sponsored the trials. Dr. Kolstad reported ties to Nordic Nanovector, Bayer Schering Pharma, Merck, and Roche.

SAN DIEGO – Rituximab can at least temporarily vanquish minimal residual disease (MRD) in mantle cell lymphoma (MCL) patients who relapse after induction therapy and autologous stem cell transplantation (ASCT), researchers reported at the annual meeting of the American Society of Hematology.

Of 58 patients whose MCL relapsed after induction therapy and ASCT, 82% converted back to an MRD-negative state after receiving 4 weekly doses of rituximab (375 mg/m²), Arne Kolstad, MD, PhD, and his associates. The data “strongly suggest that preemptive rituximab treatment delayed clinical relapse in MCL,” they wrote in their abstract. They recommended molecular and clinical monitoring after ASCT, not only “as an alternative to maintenance therapy for all MCL patients” but to identify MRD-positive candidates for clinical trials.

The study was an analysis of the Nordic Lymphoma Group phase II MCL2 and MCL3 trials (NTC 00514475), in which patients received six alternating cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) and R-Ara-C (rituximab-cytarabine). followed by high-dose ASCT. In MCL3, responders who fell short of complete remission also received intensification with yttium-90 ibritumomab tiuxetan (0.4 mCi/kg) 1 week before treatment with BEAM/C (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide). Patients were evaluated 2-3 months after completing ASCT, and then every 6 months for 5 years or until relapse. Survivors were followed for a median of 8.5 years, noted Dr. Kolstad, who is with Oslo University Hospital in Norway.

Among 183 patients who underwent polymerase chain reaction–based testing for markers of MRD, median time to molecular relapse was 55 months. However, the relapse-free survival curve did not plateau – patients in all risk groups continued to relapse 5-10 years after undergoing ASCT, the researchers said. “Hence, it is fair to consider MCL as a chronic incurable lymphoma entity, and novel approaches will be necessary to change the natural course of this disease,” they wrote.

After controlling for potential confounders, significant predictors of molecular relapse included high MCL international prognostic index at diagnosis (hazard ratio, 1.9; 95% confidence interval 1.4-2.7; P = .0001) and detection of MRD before patients underwent ASCT (HR, 2.5; 95% CI, 1.5-4.1; P = .0005). Minimal residual disease predicted clinical relapse and shorter survival (P less than .001 for both associations). In contrast, the 86 patients who remained in continuous molecular remission had a 76% chance of having at least a 10-year clinical remission, the investigators said.

Minimal residual disease was assessed by testing bone marrow and blood samples with combined standard nested and quantitative real-time polymerase chain reaction (PCR) for Bcl-1 or IgH rearrangement. They defined molecular relapse as conversion from a negative to a positive result on standard nested PCR, or, for patients who were MRD positive after ASCT, as a more than fivefold rise in real-time quantitative PCR levels in two consecutive bone marrow samples.

Oslo University sponsored the trials. Dr. Kolstad reported ties to Nordic Nanovector, Bayer Schering Pharma, Merck, and Roche.

Adjuvant chemotherapy prolonged survival after radical nephroureterectomy by nearly a year, compared with observation alone, among patients with locally advanced or positive regional lymph node upper tract urothelial carcinoma, researchers reported.

After a median follow-up period of 49 months, median overall survival was 47 months with adjuvant chemotherapy and 36 months with observation alone (P less than .001), reported Thomas Seisen, MD, of Harvard Medical School, Boston, and his associates.

This analysis included 3,253 patients with pT3/T4 and/or pN+ upper tract urothelial carcinoma from the National Cancer Database. A total of 762 (23%) patients received adjuvant chemotherapy within 90 days after surgery, while 2,491 (77%) patients underwent observation only (J Clin Oncol. 2017 Jan 3. doi: 10.1200/JCO.2016.69.414).

Kaplan Meier analyses yielded 5-year adjusted overall survival rates of 44% and 36%, respectively. Adjuvant chemotherapy conferred a significant overall survival benefit in a Cox proportional hazards regression analysis (hazard ratio, 0.77; 95% confidence interval, 0.68 to 0.88), and the effect held up in tests designed to minimize selection bias – including propensity score adjustment (HR, 0.82; 0.73 to 0.93), stratification (HR, 0.84; 0.74 to 0.95), and matching (HR, 0.84; 0.75 to 0.95).

The effect persisted across subgroups stratified by age, gender, comorbidity burden, pathologic stage, and surgical margin status, and there was no significant variability in treatment effects, the researchers said. The findings are subject to “the usual biases related to the observational study design,” but pending level 1 evidence, they inform the management of patients with advanced upper tract urothelial carcinoma who undergo radical nephroureterectomy, the researchers concluded.

The work was supported by the Vattikuti Urology Institute, the Conquer Cancer Foundation of the American Society of Clinical Oncology, and the Prostate Cancer Foundation. Dr. Seisen had no relevant financial disclosures.

[email protected]

Adjuvant chemotherapy prolonged survival after radical nephroureterectomy by nearly a year, compared with observation alone, among patients with locally advanced or positive regional lymph node upper tract urothelial carcinoma, researchers reported.

After a median follow-up period of 49 months, median overall survival was 47 months with adjuvant chemotherapy and 36 months with observation alone (P less than .001), reported Thomas Seisen, MD, of Harvard Medical School, Boston, and his associates.

This analysis included 3,253 patients with pT3/T4 and/or pN+ upper tract urothelial carcinoma from the National Cancer Database. A total of 762 (23%) patients received adjuvant chemotherapy within 90 days after surgery, while 2,491 (77%) patients underwent observation only (J Clin Oncol. 2017 Jan 3. doi: 10.1200/JCO.2016.69.414).

Kaplan Meier analyses yielded 5-year adjusted overall survival rates of 44% and 36%, respectively. Adjuvant chemotherapy conferred a significant overall survival benefit in a Cox proportional hazards regression analysis (hazard ratio, 0.77; 95% confidence interval, 0.68 to 0.88), and the effect held up in tests designed to minimize selection bias – including propensity score adjustment (HR, 0.82; 0.73 to 0.93), stratification (HR, 0.84; 0.74 to 0.95), and matching (HR, 0.84; 0.75 to 0.95).

The effect persisted across subgroups stratified by age, gender, comorbidity burden, pathologic stage, and surgical margin status, and there was no significant variability in treatment effects, the researchers said. The findings are subject to “the usual biases related to the observational study design,” but pending level 1 evidence, they inform the management of patients with advanced upper tract urothelial carcinoma who undergo radical nephroureterectomy, the researchers concluded.

The work was supported by the Vattikuti Urology Institute, the Conquer Cancer Foundation of the American Society of Clinical Oncology, and the Prostate Cancer Foundation. Dr. Seisen had no relevant financial disclosures.

[email protected]

Adjuvant chemotherapy prolonged survival after radical nephroureterectomy by nearly a year, compared with observation alone, among patients with locally advanced or positive regional lymph node upper tract urothelial carcinoma, researchers reported.

After a median follow-up period of 49 months, median overall survival was 47 months with adjuvant chemotherapy and 36 months with observation alone (P less than .001), reported Thomas Seisen, MD, of Harvard Medical School, Boston, and his associates.

This analysis included 3,253 patients with pT3/T4 and/or pN+ upper tract urothelial carcinoma from the National Cancer Database. A total of 762 (23%) patients received adjuvant chemotherapy within 90 days after surgery, while 2,491 (77%) patients underwent observation only (J Clin Oncol. 2017 Jan 3. doi: 10.1200/JCO.2016.69.414).

Kaplan Meier analyses yielded 5-year adjusted overall survival rates of 44% and 36%, respectively. Adjuvant chemotherapy conferred a significant overall survival benefit in a Cox proportional hazards regression analysis (hazard ratio, 0.77; 95% confidence interval, 0.68 to 0.88), and the effect held up in tests designed to minimize selection bias – including propensity score adjustment (HR, 0.82; 0.73 to 0.93), stratification (HR, 0.84; 0.74 to 0.95), and matching (HR, 0.84; 0.75 to 0.95).

The effect persisted across subgroups stratified by age, gender, comorbidity burden, pathologic stage, and surgical margin status, and there was no significant variability in treatment effects, the researchers said. The findings are subject to “the usual biases related to the observational study design,” but pending level 1 evidence, they inform the management of patients with advanced upper tract urothelial carcinoma who undergo radical nephroureterectomy, the researchers concluded.

The work was supported by the Vattikuti Urology Institute, the Conquer Cancer Foundation of the American Society of Clinical Oncology, and the Prostate Cancer Foundation. Dr. Seisen had no relevant financial disclosures.

[email protected]

SAN DIEGO – Late-breaking results from the phase III PERSIST-2 trial may ease at least some safety concerns surrounding the use of pacritinib in patients with myelofibrosis, investigators said at the annual meeting of the American Society of Hematology.

In February 2016, the Food and Drug Administration imposed a clinical hold on studies of pacritinib in the wake of concerns about excess deaths, cardiotoxicities, and hemorrhage. But in the final data analysis presented at ASH, rates of these outcomes were low and similar among patients randomized to pacritinib once daily, pacritinib twice daily, or best available treatment for myelofibrosis, including ruxolitinib, lead investigator John Mascarenhas, MD, said.

Indeed, more patients died of progressive disease after stopping pacritinib than died of treatment-associated adverse events, said Dr. Mascarenhas of Icahn School of Medicine at Mount Sinai, New York.

Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFS1R. In the previous phase III PERSIST-1 trial, patients who received pacritinib had a fourfold greater probability of experiencing at least a 35% decrease in splenic volume than did patients who received best available treatment (P = .003).

PERSIST-2 also yielded clear efficacy signals, particularly when patients took pacritinib twice daily, said Dr. Mascarenhas. Between baseline and week 24, splenic volume dropped by at least 35% in 22% of these patients (95% confidence interval, 13%-33%), compared with 3% of patients on best available treatment (95% CI, 0.3%-10%; P = .001). Patients who took pacritinib twice daily also had a 32% (95% CI, 22%-44%) chance of experiencing at least a 50% drop in symptoms such as fatigue, bone pain, itching, and abdominal pain, compared with 14% (95% CI, 7%-24%) of patients on best available treatment (P = .01).

Demographic and disease risk characteristics did not significantly affect the chances of reaching these coprimary endpoints, Dr. Mascarenhas noted. “My humble opinion as a clinical investigator is that [pacritinib] is an effective drug, with a favorable benefit-to-risk ratio,” he said.

Several hematologists who were not involved in this trial agreed. “I don’t see why you are nervous [about presenting these results],” noted hematologist Kanti Rai, MD, of the Feinstein Institute for Medical Research in Manhasset, N.Y., told Dr. Mascarenhas during the discussion after the data were presented, prompting laughter from the audience.

It remains to be seen whether the FDA will find the data convincing enough to lift the clinical hold on pacritinib. Ruxolitinib (Jakafi) is approved to treat splenomegaly and symptom burden in myelofibrosis but is associated with dose-limiting cytopenias and cannot be used in patients with platelet counts of less than 50,000/mcL.

PERSIST-2 compared pacritinib 400 mg once daily with pacritinib 200 mg twice daily and best available treatment, including ruxolitinib, in patients with primary or secondary myelofibrosis and less than 100,000 platelets/mcL. About half of the study patients had less than 50,000 platelets/mcL, and more than 40% had previously received ruxolitinib.

When the clinical hold on pacritinib went into effect, 221 patients had reached the 24-week designated study endpoint and were included in the intention-to-treat analysis, Dr. Mascarenhas reported. Censored Kaplan-Meier curves of overall survival favored pacritinib over best available treatment, although the difference in survival rates did not reach statistical significance (hazard ratio, 0.68; 95% CI, 0.3-1.5). A total of 9% of patients in the twice-daily pacritinib group died, compared with 14% of patients receiving pacritinib once daily or best available treatment.

Twice-daily pacritinib most often led to diarrhea (48% of patients), nausea (32%), thrombocytopenia (34%), and anemia (24%). Overall rates of serious treatment-emergent adverse events were seen in 47% of the two pacritinib groups and in 31% of patients receiving best available treatment. The most common serious treatment-emergent adverse event with twice daily pacritinib was anemia (8% of patients), followed by thrombocytopenia and pneumonia (6%). Heart failure, atrial fibrillation, and cardiac arrest were rare and similar across all three treatment groups, as were epistaxis and subdural hematoma.

This is the first randomized, controlled trial of patients with myelofibrosis and thrombocytopenia, according to Dr. Mascarenhas. “This was a patient population with low platelets and at risk of poor outcomes, and they did pretty well,” he said. “There really is no therapeutic option for patients with myelofibrosis and low platelets, and [pacritinib] offers patients in this vulnerable situation an opportunity for symptom relief. I hope to see it move forward.”

CTI Biopharma sponsored the study. Dr. Mascarenhas disclosed research funding from CTI Biopharma.

SAN DIEGO – Late-breaking results from the phase III PERSIST-2 trial may ease at least some safety concerns surrounding the use of pacritinib in patients with myelofibrosis, investigators said at the annual meeting of the American Society of Hematology.

In February 2016, the Food and Drug Administration imposed a clinical hold on studies of pacritinib in the wake of concerns about excess deaths, cardiotoxicities, and hemorrhage. But in the final data analysis presented at ASH, rates of these outcomes were low and similar among patients randomized to pacritinib once daily, pacritinib twice daily, or best available treatment for myelofibrosis, including ruxolitinib, lead investigator John Mascarenhas, MD, said.

Indeed, more patients died of progressive disease after stopping pacritinib than died of treatment-associated adverse events, said Dr. Mascarenhas of Icahn School of Medicine at Mount Sinai, New York.

Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFS1R. In the previous phase III PERSIST-1 trial, patients who received pacritinib had a fourfold greater probability of experiencing at least a 35% decrease in splenic volume than did patients who received best available treatment (P = .003).

PERSIST-2 also yielded clear efficacy signals, particularly when patients took pacritinib twice daily, said Dr. Mascarenhas. Between baseline and week 24, splenic volume dropped by at least 35% in 22% of these patients (95% confidence interval, 13%-33%), compared with 3% of patients on best available treatment (95% CI, 0.3%-10%; P = .001). Patients who took pacritinib twice daily also had a 32% (95% CI, 22%-44%) chance of experiencing at least a 50% drop in symptoms such as fatigue, bone pain, itching, and abdominal pain, compared with 14% (95% CI, 7%-24%) of patients on best available treatment (P = .01).

Demographic and disease risk characteristics did not significantly affect the chances of reaching these coprimary endpoints, Dr. Mascarenhas noted. “My humble opinion as a clinical investigator is that [pacritinib] is an effective drug, with a favorable benefit-to-risk ratio,” he said.

Several hematologists who were not involved in this trial agreed. “I don’t see why you are nervous [about presenting these results],” noted hematologist Kanti Rai, MD, of the Feinstein Institute for Medical Research in Manhasset, N.Y., told Dr. Mascarenhas during the discussion after the data were presented, prompting laughter from the audience.

It remains to be seen whether the FDA will find the data convincing enough to lift the clinical hold on pacritinib. Ruxolitinib (Jakafi) is approved to treat splenomegaly and symptom burden in myelofibrosis but is associated with dose-limiting cytopenias and cannot be used in patients with platelet counts of less than 50,000/mcL.

PERSIST-2 compared pacritinib 400 mg once daily with pacritinib 200 mg twice daily and best available treatment, including ruxolitinib, in patients with primary or secondary myelofibrosis and less than 100,000 platelets/mcL. About half of the study patients had less than 50,000 platelets/mcL, and more than 40% had previously received ruxolitinib.

When the clinical hold on pacritinib went into effect, 221 patients had reached the 24-week designated study endpoint and were included in the intention-to-treat analysis, Dr. Mascarenhas reported. Censored Kaplan-Meier curves of overall survival favored pacritinib over best available treatment, although the difference in survival rates did not reach statistical significance (hazard ratio, 0.68; 95% CI, 0.3-1.5). A total of 9% of patients in the twice-daily pacritinib group died, compared with 14% of patients receiving pacritinib once daily or best available treatment.

Twice-daily pacritinib most often led to diarrhea (48% of patients), nausea (32%), thrombocytopenia (34%), and anemia (24%). Overall rates of serious treatment-emergent adverse events were seen in 47% of the two pacritinib groups and in 31% of patients receiving best available treatment. The most common serious treatment-emergent adverse event with twice daily pacritinib was anemia (8% of patients), followed by thrombocytopenia and pneumonia (6%). Heart failure, atrial fibrillation, and cardiac arrest were rare and similar across all three treatment groups, as were epistaxis and subdural hematoma.

This is the first randomized, controlled trial of patients with myelofibrosis and thrombocytopenia, according to Dr. Mascarenhas. “This was a patient population with low platelets and at risk of poor outcomes, and they did pretty well,” he said. “There really is no therapeutic option for patients with myelofibrosis and low platelets, and [pacritinib] offers patients in this vulnerable situation an opportunity for symptom relief. I hope to see it move forward.”

CTI Biopharma sponsored the study. Dr. Mascarenhas disclosed research funding from CTI Biopharma.

SAN DIEGO – Late-breaking results from the phase III PERSIST-2 trial may ease at least some safety concerns surrounding the use of pacritinib in patients with myelofibrosis, investigators said at the annual meeting of the American Society of Hematology.

In February 2016, the Food and Drug Administration imposed a clinical hold on studies of pacritinib in the wake of concerns about excess deaths, cardiotoxicities, and hemorrhage. But in the final data analysis presented at ASH, rates of these outcomes were low and similar among patients randomized to pacritinib once daily, pacritinib twice daily, or best available treatment for myelofibrosis, including ruxolitinib, lead investigator John Mascarenhas, MD, said.

Indeed, more patients died of progressive disease after stopping pacritinib than died of treatment-associated adverse events, said Dr. Mascarenhas of Icahn School of Medicine at Mount Sinai, New York.

Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFS1R. In the previous phase III PERSIST-1 trial, patients who received pacritinib had a fourfold greater probability of experiencing at least a 35% decrease in splenic volume than did patients who received best available treatment (P = .003).

PERSIST-2 also yielded clear efficacy signals, particularly when patients took pacritinib twice daily, said Dr. Mascarenhas. Between baseline and week 24, splenic volume dropped by at least 35% in 22% of these patients (95% confidence interval, 13%-33%), compared with 3% of patients on best available treatment (95% CI, 0.3%-10%; P = .001). Patients who took pacritinib twice daily also had a 32% (95% CI, 22%-44%) chance of experiencing at least a 50% drop in symptoms such as fatigue, bone pain, itching, and abdominal pain, compared with 14% (95% CI, 7%-24%) of patients on best available treatment (P = .01).

Demographic and disease risk characteristics did not significantly affect the chances of reaching these coprimary endpoints, Dr. Mascarenhas noted. “My humble opinion as a clinical investigator is that [pacritinib] is an effective drug, with a favorable benefit-to-risk ratio,” he said.

Several hematologists who were not involved in this trial agreed. “I don’t see why you are nervous [about presenting these results],” noted hematologist Kanti Rai, MD, of the Feinstein Institute for Medical Research in Manhasset, N.Y., told Dr. Mascarenhas during the discussion after the data were presented, prompting laughter from the audience.

It remains to be seen whether the FDA will find the data convincing enough to lift the clinical hold on pacritinib. Ruxolitinib (Jakafi) is approved to treat splenomegaly and symptom burden in myelofibrosis but is associated with dose-limiting cytopenias and cannot be used in patients with platelet counts of less than 50,000/mcL.

PERSIST-2 compared pacritinib 400 mg once daily with pacritinib 200 mg twice daily and best available treatment, including ruxolitinib, in patients with primary or secondary myelofibrosis and less than 100,000 platelets/mcL. About half of the study patients had less than 50,000 platelets/mcL, and more than 40% had previously received ruxolitinib.

When the clinical hold on pacritinib went into effect, 221 patients had reached the 24-week designated study endpoint and were included in the intention-to-treat analysis, Dr. Mascarenhas reported. Censored Kaplan-Meier curves of overall survival favored pacritinib over best available treatment, although the difference in survival rates did not reach statistical significance (hazard ratio, 0.68; 95% CI, 0.3-1.5). A total of 9% of patients in the twice-daily pacritinib group died, compared with 14% of patients receiving pacritinib once daily or best available treatment.

Twice-daily pacritinib most often led to diarrhea (48% of patients), nausea (32%), thrombocytopenia (34%), and anemia (24%). Overall rates of serious treatment-emergent adverse events were seen in 47% of the two pacritinib groups and in 31% of patients receiving best available treatment. The most common serious treatment-emergent adverse event with twice daily pacritinib was anemia (8% of patients), followed by thrombocytopenia and pneumonia (6%). Heart failure, atrial fibrillation, and cardiac arrest were rare and similar across all three treatment groups, as were epistaxis and subdural hematoma.

This is the first randomized, controlled trial of patients with myelofibrosis and thrombocytopenia, according to Dr. Mascarenhas. “This was a patient population with low platelets and at risk of poor outcomes, and they did pretty well,” he said. “There really is no therapeutic option for patients with myelofibrosis and low platelets, and [pacritinib] offers patients in this vulnerable situation an opportunity for symptom relief. I hope to see it move forward.”

CTI Biopharma sponsored the study. Dr. Mascarenhas disclosed research funding from CTI Biopharma.

SAN DIEGO – Dual therapy with lenalidomide and epoetin alfa was safe and led to freedom from transfusion significantly more often than lenalidomide alone in patients with erythropoietin-refractory, lower-risk, non-del(5q) myelodysplastic syndromes, according to a randomized phase III head-to-head trial.

After 16 weeks of treatment, 33% of patients who received both lenalidomide and epoetin alfa met International Working Group 2000 criteria for major erythroid response, compared with only 14% of patients receiving lenalidomide monotherapy (P = .03), Alan F. List, MD, reported at the annual meeting of the American Society of Hematology.

H. Lee Moffitt Cancer Center

SAN DIEGO – Dual therapy with lenalidomide and epoetin alfa was safe and led to freedom from transfusion significantly more often than lenalidomide alone in patients with erythropoietin-refractory, lower-risk, non-del(5q) myelodysplastic syndromes, according to a randomized phase III head-to-head trial.

After 16 weeks of treatment, 33% of patients who received both lenalidomide and epoetin alfa met International Working Group 2000 criteria for major erythroid response, compared with only 14% of patients receiving lenalidomide monotherapy (P = .03), Alan F. List, MD, reported at the annual meeting of the American Society of Hematology.

H. Lee Moffitt Cancer Center

SAN DIEGO – Dual therapy with lenalidomide and epoetin alfa was safe and led to freedom from transfusion significantly more often than lenalidomide alone in patients with erythropoietin-refractory, lower-risk, non-del(5q) myelodysplastic syndromes, according to a randomized phase III head-to-head trial.

After 16 weeks of treatment, 33% of patients who received both lenalidomide and epoetin alfa met International Working Group 2000 criteria for major erythroid response, compared with only 14% of patients receiving lenalidomide monotherapy (P = .03), Alan F. List, MD, reported at the annual meeting of the American Society of Hematology.

H. Lee Moffitt Cancer Center

SAN DIEGO – Adding daratumumab (D) to lenalidomide and dexamethasone (Rd) significantly improved outcomes in relapsed and refractory multiple myeloma, even when patients had previously received lenalidomide, were refractory to bortezomib, or had high-risk tumor cytogenetics, based on updated analyses from the multicenter, randomized, phase III, open-label POLLUX trial.

The findings underscore the “significant benefit of combining daratumumab with lenalidomide and dexamethasone for relapsed or refractory multiple myeloma,” said lead investigator Philippe Moreau, MD, of University Hospital Hotel-Dieu in Nantes, France.

Amy Karon/Frontline Medical News

SAN DIEGO – Adding daratumumab (D) to lenalidomide and dexamethasone (Rd) significantly improved outcomes in relapsed and refractory multiple myeloma, even when patients had previously received lenalidomide, were refractory to bortezomib, or had high-risk tumor cytogenetics, based on updated analyses from the multicenter, randomized, phase III, open-label POLLUX trial.

The findings underscore the “significant benefit of combining daratumumab with lenalidomide and dexamethasone for relapsed or refractory multiple myeloma,” said lead investigator Philippe Moreau, MD, of University Hospital Hotel-Dieu in Nantes, France.

Amy Karon/Frontline Medical News

SAN DIEGO – Adding daratumumab (D) to lenalidomide and dexamethasone (Rd) significantly improved outcomes in relapsed and refractory multiple myeloma, even when patients had previously received lenalidomide, were refractory to bortezomib, or had high-risk tumor cytogenetics, based on updated analyses from the multicenter, randomized, phase III, open-label POLLUX trial.

The findings underscore the “significant benefit of combining daratumumab with lenalidomide and dexamethasone for relapsed or refractory multiple myeloma,” said lead investigator Philippe Moreau, MD, of University Hospital Hotel-Dieu in Nantes, France.

Amy Karon/Frontline Medical News