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The most common treatment-related AEs included fatigue ( 26 %), pyrexia ( 24 %), cough ( 24 %), musculoskeletal pain ( 21 %), diarrhea ( 20 %), and rash ( 20 %). Serious AEs occurred in 16 percent of patients , the most common of which were pneumonia , pneumonitis , pyrexia , dyspnea , graft-versushost disease ( GVHD ), and herpes zoster .
Five percent of patients discontinued therapy because of AEs , and 26 percent experienced treatment interruption . Two patients died from GVHD after subsequent allogeneic HCT and septic shock .
Source : Merck news release , March 14 , 2017 .
FDA Approves Lenalidomide for Maintenance Therapy in Multiple Myeloma
The U . S . Food and Drug Administration ( FDA ) expanded the approval of lenalidomide to include maintenance therapy for patients with multiple myeloma ( MM ) who have received autologous hematopoietic cell transplantation ( AHCT ).
The approval was based on the results of two studies that compared lenalidomide maintenance therapy versus no maintenance in more than 1,000 patients .
The double-blind , randomized , phase III CALGB 100104 study was conducted at 47 U . S . centers and randomized patients to receive maintenance lenalidomide ( started at 10 mg daily and elevated to 15 mg daily at three months if tolerated ) or placebo after firstline chemotherapy and AHCT . The median progression-free survival ( PFS ; primary endpoint ) was 5.7 years among those who received lenalidomide maintenance therapy , compared with 1.9 years for those who did not ( hazard ratio [ HR ] = 0.38 ; 95 % CI 0.28-0.5 ). Overall survival ( OS ) was also significantly improved in those treated with lenalidomide therapy , with a median of 9.3 years versus 7.0 years ( HR = 0.59 ; 95 % CI 0.44-0.78 ).
The double-blind , phase III IFM 2005-02 study was conducted at 78 centers in Belgium , France , and Switzerland and included treatment-naïve patients who had previously received induction chemotherapy and AHCT . They were randomized 1:1 to receive consolidation lenalidomide
( 25 mg / day on days 1-21 of each 28-day cycle for two cycles ) followed by placebo or maintenance lenalidomide ( 10 mg / day induction dose increased to 15 mg / day at three months if tolerated ). The median PFS ( primary endpoint ) was 3.9 years among those who received lenalidomide maintenance therapy , compared with 2.0 years for those who did not ( HR = 0.53 ; 95 % CI 0.44- 0.64 ). The OS benefit with lenalidomide maintenance therapy was slightly better , but not significantly so : 8.8 years versus 7.3 years ( HR = 0.90 ; 95 % CI 0.72-1.13 ).
The most common adverse events ( AEs ) associated with lenalidomide maintenance therapy in the first and second studies included neutropenia ( 79 % and 61 %), thrombocytopenia ( 72 % and 24 %), leukopenia ( 23 % and 32 %), anemia ( 21 % and 9 %), upper respiratory tract infection ( 27 % and 11 %), bronchitis ( 5 % and 47 %), nasopharyngitis ( 2 % and 35 %), cough ( 10 % and 27 %), gastroenteritis ( 0 % and 23 %), diarrhea ( 55 % and 39 %), rash ( 32 % and 8 %), and fatigue ( 23 % and 11 %). The most common grade 3 / 4 AEs were neutropenia , thrombocytopenia , and leukopenia .
Hematologic secondary primary malignancies occurred in 7.5 percent of patients who received lenalidomide maintenance therapy and 3.3 percent of patients who did not ( p value not reported ).
Source : U . S . Food and Drug Administration press release , February 22 , 2017 .
FDA Approves Pembrolizumab for Classic Hodgkin Lymphoma
The FDA approved the anti-PD-1 monoclonal antibody pembrolizumab for adults and children with classic Hodgkin lymphoma who are refractory to treatment or who have relapsed after receiving ≥3 prior lines of therapy . This is the only anti-PD-1 therapy approved for this patient population .
The approval was based on results from the KEYNOTE-087 trial , which included 210 patients who received pembrolizumab 200 mg every three weeks . Many patients ( 58 %) were refractory to their previous therapy , including 35 percent who had primary-refractory disease and 14 percent whose disease was chemotherapy-refractory to all prior regimens . Prior treatments included hematopoietic cell transplantation ( HCT ; 61 %) and radiation therapy ( 36 %); 17 percent of patients had not received brentuximab vedotin .
After a median follow-up of 9.4 months , the overall response rate ( ORR ) was 69 percent ( 95 % CI 62-75 ), which included a complete remission rate of 22 percent and a partial remission rate of 47 percent . The median duration of response among the 145 patients who responded to therapy was 11.1 months ( range = 0-11.1 months ).
FDA Grants Priority Review of Enasidenib for Acute Myeloid Leukemia
The FDA granted priority review of enasidenib for patients with relapsed / refractory IDH2-mutated acute myeloid leukemia ( AML ).
The decision was based on results of the single-arm , phase I / II AG221- C-001 study , which included 198 patients ( median age = 69 years ) with relapsed / refractory AML ( 70 %), untreated AML ( 17 %), myelodysplastic syndromes ( 7 %), or another IDH2-mutant hematologic malignancy ( 6 %). Patients received a median of two prior therapies ( range = 1-6 therapies ), and 64 percent received ≥2 prior therapies . Enasidenib was administered at escalating doses , increasing from 30 mg or 50 mg once or twice daily to the highest dose of 450 mg daily . Though a maximum tolerated dose was not reached , the dose selected for future studies was 100 mg once daily .
Among 181 evaluable patients ( including 128 with relapsed / refractory AML ), the objective response rate was 41 percent in enasidenib-treated patients . The complete response ( CR ) rate was 18 percent , with 1.6 percent of patients achieving a CR with incomplete platelet recovery or incomplete blood count recovery . Fourteen percent of patients had a partial response ( PR ).
The median duration of response was 6.9 months ; in those with relapsed / refractory AML , the median duration was six months ( 95 % CI 3.7-9.2 ).
Overall , eight patients went on to receive HCT , five of whom had relapsed / refractory AML . The most common treatment-related AEs were indirect hyperbilirubinemia ( 19 %) and nausea ( 18 %).
Source : Celgene press release , March 1 , 2017 .
20 ASH Clinical News May 2017