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PURPOSE Chronic graft-versus-host disease (cGVHD) remains the major cause of late morbidity after allogeneic hematopoietic cell transplantation. Colony-stimulating factor 1 receptor (CSF-1R)–dependent macrophages promote cGVHD fibrosis, and their elimination in preclinical studies ameliorated cGVHD. Axatilimab is a humanized monoclonal antibody that inhibits CSF-1R signaling and restrains macrophage development. PATIENTS AND METHODS This phase I (phI)/phase II (phII) open-label study (ClinicalTrials.gov identifier: NCT03604692 ) evaluated safety, tolerability, and efficacy of axatilimab in patients age ≥ 6 years with active cGVHD after ≥ 2 prior systemic therapy lines. Primary objectives in phI were to identify the optimal biologic and recommended phII dose and in phII to evaluate the overall (complete and partial) response rate (ORR) at the start of treatment cycle 7. RESULTS Forty enrolled patients (17 phI; 23 phII) received at least one axatilimab dose. In phI, a dose of 3 mg/kg given once every 4 weeks met the optimal biologic dose definition. Two dose-limiting toxicities occurred at the 3 mg/kg dose given once every 2 weeks. At least one treatment-related adverse event (TRAE) was observed in 30 patients with grade ≥ 3 TRAEs in eight patients, the majority known on-target effects of CSF-1R inhibition. No cytomegalovirus reactivations occurred. With the 50% ORR at cycle 7 day 1, the phII cohort met the primary efficacy end point. Furthermore, the ORR in the first six cycles, an end point supporting regulatory approvals, was 82%. Responses were seen in all affected organs regardless of prior therapy. Fifty-eight percent of patients reported significant improvement in cGVHD-related symptoms using the Lee Symptom Scale. On-target activity of axatilimab was suggested by the decrease in skin CSF-1R–expressing macrophages. CONCLUSION Targeting profibrotic macrophages with axatilimab is a therapeutically promising novel strategy with a favorable safety profile for refractory cGVHD.

11607 Background: Melphalan, remains the mainstay of conditioning for autologous hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) patients. Gastrointestinal symptoms represent the most significant non-hematologic toxicities following high-dose melphalan conditioning, with approximately 40% of patients experiencing CTCAE grade 2 or higher diarrhea following conditioning regimens containing melphalan. Enterade is a proprietary blend of electrolytes and five amino-acids that can facilitate retention of the absorbing capacity of the small intestine by rebuilding the villi and reduce antigenic translocation by tightening the mucosal barrier. In a study of irradiated mice, enterade improved survival and improved body weight following irradiation. The goal was to investigate the effectiveness of enterade to reduce GI toxicities after high-dose melphalan chemotherapy. Methods: The trial was designed as a Phase 2, multi-center, double-blinded, 2-arm randomized study. 114 MM or NHL patients were enrolled between October 2016 and October 2017. Patients received either two 8oz bottles/day of enterade or placebo starting on the day of admission through Day +14. GI toxicity was scored by the CT-CAE 4.0 system from admission through Day + 14. Compliance was arbitrarily set at consumption of 2 bottles daily for 11+ days. Results: Of the 114 enrolled patients, 99 (61 MM, 38 NHL) attempted to consume at least 1 dose of enterade/placebo. Compliance overall was much lower than anticipated; with no MM patients achieving compliance compared to 34.2% in the NHL group. Compliance in NHL patients was 31.6% in the enterade group versus 36.8% in the placebo group. Analysis of primary endpoint in NHL patients showed a 16% incidence of diarrhea ≥ grade 2 in enterade compliant patients versus 86% in the placebo group (p= 0.02). Conclusions: Eleven days of two 8oz bottles of liquid is a difficult task during ASCT, especially for MM with nausea, altered taste and poor appetite. For those NHL patients, compliant per protocol (who consumed ≥11 days), enterade significantly reduced diarrhea. The use of enterade to prevent diarrhea following high-dose chemotherapy should be explored further in populations capable of reasonable oral intake. Clinical trial information: NCT02919670.

e19003 Background: High-dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high-risk lymphoma. Elderly patients, who make up an increasing proportion of lymphoma patients, are often not considered candidates due to concern for excess toxicity and mortality. However, preliminary reports suggest that ASCT in carefully selected elderly patients can be feasible, safe, and effective. Methods: We identified patients ≥70 years of age with Hodgkin or non-Hodgkin lymphoma who underwent ASCT between 2000 and 2016 at two partner institutions. We recorded clinical characteristics, lymphoma diagnosis, conditioning regimen; and outcomes regarding engraftment, treatment toxicities, and relapse. Kaplan-Meier survival analysis for overall and relapse-free survival was performed. Results: 119 elderly patients with lymphoma who were treated with ASCT were identified. Median age at transplant was 72 (range, 70-79). The most common lymphoma subtype was diffuse large B-cell (n=75, 63%); others were T-cell (n=19), mantle cell (n=12), follicular (n=7), and Hodgkin (n=6). Conditioning regimens included BEAM (BCNU, etoposide, Ara-C, melphalan), CBV (cyclophosphamide, BCNU, etoposide), and Bu/Cy (busulfan/cyclophosphamide). Median time to neutrophil recovery (ANC>500) and platelet recovery (>20,000) were 10 and 12 days, respectively. Three patients had early mortality (within 100 days) from rapid disease progression (n=1) or treatment toxicity (n=2). Median follow up for survivors was 23 months (range, 0-157). Two-year progression-free survival and overall survival were 58% (95%CI, 48-67%) and 66% (95%CI, 55-74%), respectively. The leading cause of treatment failure was disease relapse, which occurred in 33% of patients (n=39). Two-year estimate for non-relapse mortality was 7% (95%CI, 3-14%). Conclusions: ASCT is safe and feasible in selected elderly lymphoma patients, although relapse and non-relapse mortality may be higher than in younger patients. Eligibility for ASCT should be an individualized decision, and age should not be an absolute barrier to ASCT referral in healthy elderly patients with lymphoma.