ASH Clinical News ACN_5.4s_March_supplement_web - Page 18

MEETING NEWS are more likely to derive benefit from salvage transplant than continuous Rd, including those with: • revised ISS stage I disease (HR=0.08 for OS [p=0.02]) • standard-risk cytogenetics (HR=0.21 for OS [p=0.01]) There also were no significant differences in survival benefit according to “traditional risk factors,” like baseline ISS, age, renal function, response to reinduction, prior therapy lines, and single or tandem frontline AHCT. Although these data should provide guidance on the choice between salvage AHCT or continuous Rd therapy in patients with relapsed MM, they suggest that its value may not be as high as previously assumed. Dr. Goldschmidt noted that the trial had better-than-expected efficacy in the Rd control arm. Dr. Baertsch added that the comparator in this trial (Rd) was not one of the more effective triplet regimens that have now become standard of care for relapsed MM, so definite conclusions on the role of salvage AHCT in [the modern era] cannot be drawn.” The ReLApsE investigators report relationships with Celgene, the manufacturer of lenalidomide. REFERENCES 1. Goldschmidt H, Baertsch M-A, Schlenzka J, et al. Salvage autologous transplant and lenalidomide maintenance versus continuous lenalidomide/dexamethasone for relapsed multiple myeloma: results of the randomized GMMG phase III multicenter trial relapse. Abstract #253. Presented at the 2018 ASH Annual Meeting, December 1, 2018; San Diego, CA. 2. Baertsch M-A, Schlenzka J, Habermehl C, et al. Subgroup analyses of the randomized GMMG phase III multicenter trial relapse suggest survival benefit of salvage autologous transplant primarily in low risk multiple myeloma. Abstract #254. Presented at the 2018 ASH Annual Meeting, December 1, 2018; San Diego, CA. Venetoclax Plus R-CHOP Improves Outcomes in BCL2-Positive DLBCL For the substantial portion of patients with diffuse large B-cell lymphoma (DLBCL) with overexpression of the BCL2 protein, com- bining the BCL2 inhibitor venetoclax with standard chemotherapy may improve response rates, according to results from the phase II CAVALLI trial. However, patients who received venetoclax ex- perienced a higher rate of adverse events (AEs) compared with a historical control group who received chemotherapy alone. In the CAVALLI trial, investigators, led by Franck Morschhauser MD, PhD, of Centre Hospitalier Régional Universitaire in Lille, France, studied the safety and efficacy of venetoclax plus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), then compared these outcomes with controls in the phase III GOYA trial who received R-CHOP alone. (GOYA compared anti-CD20 16 Focus on Lymphoid Malignancies monoclonal antibody obinutuzumab versus rituximab in addition to CHOP chemotherapy in patients with previously untreated DLBCL). The present study included 208 adults with DLBCL, an Inter- national Prognostic Index score of 2 to 5, an Eastern Cooperative Oncology Group performance status of ≤2, and at least one mea- surable lesion ≥1.5 cm. Patients were assigned to receive six cycles of R-CHOP plus venetoclax (800 mg on days 4-10 of cycle 1, and days 1-10 of cycles 2-8). Per study protocol, two additional cycles of vene- toclax plus rituximab were permitted per physician choice. CAVALLI participants were matched with 564 patients from the GOYA trial. Patient characteristics were well matched, Dr. Morschhauser noted, except for a larger number of patients with higher-stage disease and BCL2 immunohistochemistry (IHC)- positive disease in the CAVALLI group. The complete response (CR) rates (primary endpoint) did not differ significantly between the two cohorts: 69.2 percent versus 62.8 percent, respectively (95% CI 0-17.6). However, venetoclax appeared to improve CR rates among patients with BCL2-positive disease and double-hit lymphoma ( TABLE , opposite page). After a median follow-up of 20 months in the CAVALLI trial, 29 patients had died and six experienced disease progression. These findings suggest that venetoclax improved progression-free survival (PFS) for patients with BCL2 IHC-positive disease, compared with those treated with R-CHOP alone in the GOYA trial (hazard ratio = 0.53; 95% CI 0.30-0.93). There was, however, no PFS benefit observed in BCL2 IHC-negative subgroups. Each regimen was associated with distinct AE profiles, Dr. Morschhauser said. CAVALLI participants experienced a higher rate of grade 3/4 AEs, compared with GOYA participants: 85 per- cent (n=176/208) and 66 percent (n=373/574), respectively. The higher toxicity rate in CAVALLI was driven largely by hematologic events, including (p values not reported): • neutropenia: 64.9% vs. 38.8% • thrombocytopenia: 23.6% vs. 1.5% • anemia: 22.1% vs. 8.9% • febrile neutropenia: 33.2% vs. 16.3% • infections: 22.6% vs. 16.0% Infections were all bacterial, with no recorded pneumocystis or fungal infections. More patients in the CAVALLI trial required dose interruptions or discontinuations of either venetoclax or R-CHOP. The research- ers noted, however, that the higher toxicity seen in the venetoclax- treated patients did not lead to an increase in treatment-related mortality, as the rate of AEs with fatal outcomes was 2 percent in CAVALLI versus 5 percent in GOYA (p value not reported). The authors concluded that venetoclax added to R-CHOP improved efficacy in patients with BCL2 IHC-positive DLBCL and that these findings support exploration of this combination in high- risk populations of patients with BCL2-positive DLBCL, including