In July, the United States Food and Drug Administration (FDA) approved four new indications for cancer treatment, three of them are for hematologic malignancies.

Expanded Indication for Atezolizumab for BRAF-Mutant Advanced Melanoma in Combination with Targeted Therapy.

Atezolizumab (Tecentriq®, Genentech Inc.) plus the combination of MEK inhibitor cobimetinib and BRAF inhibitor vemurafenib (Cotellic® and Zelboraf®, Genentech Inc.) received approval for the first-line treatment of patients with BRAF V600 mutation-positive unresectable advanced melanoma. Efficacy results from the multicenter, double-blind, randomized, placebo-controlled phase III trial IMspire150 supported the approval. A total of 514 patients were assigned to 28-day cycles of either atezolizumab, vemurafenib and cobimetinib, or placebo, vemurafenib and cobimetinib. The primary efficacy outcome was investigator-assessed progression-free survival (PFS); median PFS was 15.1 months in the atezolizumab arm versus 10.6 months in the placebo arm (hazard ratio [HR] 0.78; P=0.0249).

Tafasitamab First Approval in Combination with Lenalidomide for Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL).

An accelerated approval was grantedto an anti-CD19 monoclonal antibody tafasitamab-cxix (Monjuvi®, MorphoSys US Inc.) in combination with lenalidomide for patients with R/R DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, who are ineligible for autologous stem cell transplant. The approval was based on results from the multicenter, open-label, single-arm phase II L-MIND study that enrolled 81 patients. Patients received intravenous tafasitamab (12 mg/kg intravenously) and oral lenalidomide (25 mg orally, on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab monotherapy until disease progression. Best overall response rate (ORR) per independent review committee (IRR) was the primary endpoint of the study, and response duration (DOR) was a key secondary endpoint. The best ORR in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with 37% achieving a complete response (CR) and 18% achieving a partial response (PR). Median DOR was 21.7 months. The most common treatment-emergent adverse events of grade ≥3 were neutropenia, thrombocytopenia, and febrile neutropenia.

CAR T Brexucabtagene Autoleucel for Patients with R/R Mantle Cell Lymphoma (MCL).

Accelerated approval was granted to brexucabtagene autoleucel (Tecartus™, Kite, a Gilead Company), the first and only chimeric antigen receptor (CAR) T cell therapy for the treatment of patients with R/R MCL. The approval was based on efficacy results from the multicenter, single-arm, open-label phase II ZUMA-2 study that enrolled 74 patients with R/R MCL, who had received up to 5 previous therapies. Patients received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy. The primary endpoint was ORR per IRR, and the primary efficacy analysis was performed after 60 patients had been treated and followed-up for at least 7 months. The ORR was 93% with a CR rate of 67%. The median DOR was not reached. Among all 74 enrolled patients, the ORR per IRR, was 85% with a CR rate of 59%. Note, the approval is accompanied by a Risk Evaluation and Mitigation Strategy due to the risk of cytokine release syndrome and neurologic toxicities.

An Oral Fixed-Dose Combination of Decitabine and Cedazuridine for Myelodysplastic Syndromes (MDS).

Decitabine was approved in combination with cedazuridine (INQOVI, Astex Pharmaceuticals, Inc.) for patients with previously treated and untreated de novo and secondary MDS with the following subtypes (French-British classification): refractory anemia (RA), RA with ringed sideroblasts, RA with excess blasts and chronic myelomonocytic anemia (CMML) and those with intermediate-1, intermediate-2 and high risk International Prognostic Scoring System (IPPS) disease. Approval was based on data from 2 open label, randomized, crossover trials, ASTX727-01B and ASTX727-02 that included a total of 213 patients. In both trials, patients were randomized to receive either the fixed dose of oral combination of decitabine and cedazuridine in cycle 1 (35 mg decitabine and 100 mg cedazuridine) and intravenous decitabine in cycle 2 (20 mg/m²), or the reverse sequence. Both treatments were administered once daily on days 1 through to 5 of a 28-day cycle. Complete responses (CR) were demonstrated in 18% and 21% of patients in trials -01B and -02, respectively. Median duration of CR was 8.7 months and 7.5 months. For those patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 49% and 53% of patients became independent during any consecutive 56-day post-baseline period in trial -01B and in -02, respectively. For patients who were independent of RBC and/or platelet transfusions at baseline, 64% and 63% remained independent, respectively. The overall safety profile of the oral combination was similar to intravenous decitabine.