Optimizing Post-Allogeneic Hematopoietic Cell Transplant Outcomes For Lymphoma Using Ibrutinib: Early Safety Results Of A Multicenter Study

Background Ibrutinib is approved for a variety of B-cell malignancies, including CLL and MCL, and for chronic GVHD (cGVHD), failing ≥ 1 line of systemic therapy. Allogeneic HCT is curative for CLL and MCL, but success is limited due to relapse or GVHD morbidity/mortality. We hypothesized that use of ibrutinib early post HCT would optimize outcomes by improving progression-free survival (primary outcome) and decrease incidence of moderate-severe cGVHD (secondary endpoint). We describe our findings regarding safety and feasibility in the first 16 patients (NCT02869633). Methods Adult patients (pts) undergoing T-replete HCT from related or unrelated donors (7/8 or 8/8) without post-transplant cyclophosphamide for CLL (u003eCR1, or after 1 st line if 17p) or MCL (u003eCR1, or after 1 st line if blastoid variant) were enrolled, along with an exploratory cohort of FL and HL (max 10 patients). Use of ibrutinib prior to HCT was permissible. Enrollment was prior to HCT, but pts had to meet secondary eligibility criteria to ensure no critical illness, adequacy of graft and organ function, prior to starting ibrutinib (420 mg daily) between day 60-90. Ibrutinib was continued until 12 m post HCT. Results Sixteen pts (CLL 44%, MCL 13%, FL 25%, HD 13%), median age 49.5 y, underwent HCT from unrelated (94%) or related donors (6%), that were 8/8 (88%) or 7/8 (12%) HLA matched, at a median of 30.2 m after diagnosis. Median follow up from HCT is 5.1 m and 1 y survival is 75%. Regimens included FCR-thymoglobulin (44%), TLI-ATG (31%), Flu Bu (13%) or Flu Mel (12%). GVHD prophylaxis was tacrolimus-MTX (69%) or CSA-MMF (31%). Of the 14 pts eligible to start ibrutinib (u003e 60 d post HCT), 9 started ibrutinib (64%), while 5 did not (4-not meet secondary eligibility criteria, 1-physician preference). The median starting dose was 140 mg (protocol specified due to drug interactions). Of the 9 pts who started ibrutinib, 2 (22%) had to stop it prematurely (cytopenias, confounded by concomitant medications), 3 (33%) completed therapy and 4 (45%) are on therapy. Table 1 outlines key ≥ grade 3 adverse events (AEs) at any time point after enrollment. In this group of 9 pts, aGVHD grade 0, 1, 3 and 4 was seen in 57%, 22%, 7% and 14%, and cGVHD was seen in 3 pts (7%-mild, 14%-severe). No pts had progression of disease (CR-67%, PR-11%, SD-22%); 2 pts are deceased (1-infection at 14 m post HCT in CR, and 1 from acute GVHD (onset prior to start of ibrutinib with SD). Conclusions Our data in this ongoing study shows that majority of patients could initiate early post HCT ibrutinib and most are expected to tolerate it until 1 y post HCT. No unexpected side effects have been seen with use of ibrutinib early post HCT, and there have been no relapses.