Purpose

We previously reported a 44% overall response rate (ORR) with the oral BCL-2 inhibitor venetoclax in a phase I study of relapsed/refractory non-Hodgkin lymphoma (NHL). Complete response (CR) was observed in patients with mantle cell lymphoma [(MCL), 21%, n = 6/28] and follicular lymphoma [(FL), 17%, n = 5/29], and partial response (PR) noted in several patients with Waldenström macroglobulinemia (WM), and marginal zone lymphoma (MZL). Here, we report the long-term outcomes of these four cohorts.

Patients and methods

All patients (n = 106) received venetoclax monotherapy in dose cohorts of 200 to 1,200 mg daily until disease progression or unacceptable toxicity. ORR, progression-free survival (PFS), duration of response (DoR), and adverse events (AEs) were evaluated.

Results

At a median follow-up of 38.5 months (range, 30.0-46.5), the median PFS for all 106 patients was 5.4 [95% confidence interval (CI), 3.5-8.4] months (FL, 10.8; MCL, 11.3; MZL, 21.2; and WM, 30.4). The median DoR was 14.9 (95% CI, 9.7-27.6) months (FL, 26.6; MCL, 15.7; MZL, 20.1; and WM, 25.3). Achievement of CR versus PR predicted longer DoR in both MCL (31.5 vs. 10.1 months) and FL (37.6 vs. 9.7 months). All grade hematologic AEs were infrequent: neutropenia (19%), anemia (19%), and thrombocytopenia (17%), with no new cytopenias after 2 years on therapy. Nonhematologic AEs included nausea (49%), diarrhea (46%), fatigue (44%), with decreased incidence after 1 year.

Conclusions

Venetoclax monotherapy has a manageable safety profile and achieves durable responses in a subset of patients with FL, MCL, WM, and MZL, particularly in those who achieve CR. Further research is warranted on combination strategies to enhance the durability of response to venetoclax.

The application of allogeneic hematopoietic cell transplantation (allo-HCT) in non-Hodgkin lymphoma (NHL) patients ≥65 years in the United States is limited by lack of Medicare coverage for this indication. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report allo-HCT outcomes of NHL patients aged ≥65 years (older cohort; n = 446) compared with a cohort of younger NHL patients aged 55-64 years (n = 1183). We identified 1629 NHL patients undergoing a first reduced-intensity conditioning (RIC) or nonmyeloablative conditioning allo-HCT from 2008 to 2015 in the United States. Cord blood or haploidentical transplants were excluded. The median age was 68 years (range 65-77) for the older cohort vs 60 years (range 55-64) in the younger cohort. The 4-year adjusted probabilities of nonrelapse mortality (NRM), relapse/progression (R/P), progression-free survival (PFS), and overall survival (OS) of the younger and older groups were 24% vs 30% (P = .03), 41% vs 42% (P = .82), 37% vs 31% (P = .03), and 51% vs 46% (P = .07), respectively. Using multivariate analysis, compared with the younger group, the older cohort was associated with increased NRM, but there was no difference between the 2 cohorts in terms of R/P, PFS, or OS. The most common cause of death was disease relapse in both groups. In NHL patients eligible for allo-HCT, there was no difference in OS between the 2 cohorts. Age alone should not determine allo-HCT eligibility in NHL, and Medicare should expand allo-HCT coverage to older adults.