Epcoritamab-Bysp for R/R Diffuse Large B-Cell Lymphoma & High-Grade B-Cell Lymphoma
Epcoritamab-bysp received accelerated approval for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy.
Epcoritamab-bysp, a bispecific CD20-directed CD3 T-cell engager, was evaluated in EPCORE NHL-1 (NCT03625037), an open-label, multi-cohort, multicenter, single-arm trial in patients with relapsed or refractory B-cell lymphoma. The efficacy population consisted of 148 patients with relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy, including at least one anti-CD20 monoclonal antibody-containing therapy.
The main efficacy outcome measure was overall response rate (ORR) determined by Lugano 2014 criteria, as assessed by an Independent Review Committee. The ORR was 61 percent (95% CI: 53, 69) with 38 percent of patients achieving complete responses. With a median follow-up of 9.8 months among responders, the estimated median duration of response (DOR) was 15.6 months (95% CI: 9.7, not reached).
The prescribing information has a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS) and life-threatening for fatal immune effector cell-associated neurotoxicity syndrome (ICANS). Warnings and precautions include infections and cytopenias. Among the 157 patients with relapsed or refractory large B-cell lymphoma who received epcoritamab-bysp at the recommended dose, CRS occurred in 51 percent of patients, ICANS in 6 percent, and serious infections in 15 percent. For CRS, Grade 1 occurred in 37 percent of patients, Grade 2 in 17 percent, and Grade 3 in 2.5 percent. For ICANS, Grade 1 occurred in 4.5 percent, Grade 2 in 1.3 percent, and Grade 5 in 0.6 percent.
Epcoritamab-bysp should only be administered by a qualified health care professional with appropriate medical support to manage severe reactions, such as CRS and ICANS. Because of the risk of these reactions, patients should be hospitalized for 24 hours after the Cycle 1, Day 15 dosage of 48 mg. The most common (>=20%) adverse reactions were CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common Grade 3-4 laboratory abnormalities (>=10%) were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.
The recommended regimen consists of epcoritamab-bysp administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity. The recommended dose is step-up dosing in Cycle 1 (0.16 mg on Day 1, 0.8 mg on Day 8, and 48 mg on Day 15 and Day 22) followed by fixed dosing of 48 mg weekly dosing during Cycles 2 through 3, every other week during Cycle 4 through 9, and then every 4 weeks on Day 1 of subsequent cycles.
Olaparib With Abiraterone & Prednisone/Prednisolone for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer
The FDA approved olaparib with abiraterone and prednisone (or prednisolone) for adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.
Efficacy was evaluated in the PROpel trial (NCT03732820) that enrolled 796 patients with mCRPC. Patients were randomized (1:1) to receive either olaparib with abiraterone or placebo with abiraterone and also received prednisone or prednisolone. Patients were required to have a prior orchiectomy and, if not performed, received gonadotropin-releasing hormone (GnRH) analogs.
Patients with prior systemic therapy for mCRPC were excluded; however, prior docetaxel for metastatic hormone-sensitive prostate cancer was allowed. Randomization was stratified by site of metastases and prior docetaxel. All available clinical samples were retrospectively tested for BRCA mutational status with the FoundationOne CDx and FoundationOne Liquid CDx tests.
The major efficacy outcome measure was investigator-assessed radiological progression-free survival (rPFS) per RECIST version 1.1 for soft tissue and Prostate Cancer Working Group criteria for bone lesions. Overall survival (OS) was an additional endpoint.
A statistically significant improvement in rPFS for olaparib with abiraterone compared to placebo with abiraterone in the intent-to-treat (ITT) population was observed. An exploratory subgroup analysis in the 85 patients with BRCAm (11% of ITT population) demonstrated a median rPFS that was not reached in the olaparib with abiraterone arm compared to 8 months (95% CI: 6, 15) for those receiving placebo with abiraterone (HR: 0.24 [95% CI: 0.12, 0.45]). The OS HR in these patients was 0.30 (95% CI: 0.15, 0.59). In the 711 patients (89% of ITT population) without BRCAm, the rPFS HR was 0.77 (95% CI: 0.63, 0.96) and the OS HR was 0.92 (95% CI: 0.74, 1.14), suggesting that the improvement in rPFS observed in the ITT population was primarily attributable to patients with BRCAm.
The most common adverse reactions (>=10%) in patients receiving olaparib plus abiraterone were anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%). Seventy-two patients (18%) required at least one blood transfusion and 46 (12%) required multiple transfusions.
The recommended olaparib dose is 300 mg taken orally twice daily with or without food. The recommended abiraterone dose is 1,000 mg taken orally once daily. Abiraterone should be administered with prednisone or prednisolone 5 mg orally twice daily. Patients should also receive a GnRH analog concurrently or should have had a prior bilateral orchiectomy.