PS1396 RESULTS OF PHASE I/II STUDY OF NIVOLUMAB WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA PATIENTS WITH SUBOPTIMAL RESPONSE TO PRIMARY INDUCTION THERAPY

Background: Patients with multiple myeloma (MM) who do not achieve complete response (CR) or very good partial response (VGPR) after primary therapy, including autologous hematopoietic stem cell transplantation (ASCT), have short time to progression. Preclinical and clinical evidence suggests that the immune checkpoint programmed death‐1 (PD‐1) receptor/PD‐1 ligand axis plays an important role in suppressing immune surveillance against MM, but monotherapy with anti‐PD‐1 antibody was not effective in patients with MM. We hypothesized that the administration of nivolumab (an anti‐PD‐1 antibody) during the lymphodepleted state post‐ASCT can improve therapeutic efficacy in MM. Aims: To evaluate the efficacy and safety of the checkpoint inhibitor nivoluumab in combination with ASCT. Methods: We conducted a phase 1–2, single‐arm study nivolumab with ASCTin MM patients who had not achieved pre‐AHCT less than VGPR after induction therapy (NCT03292263). Nivolumab was administered 100 mg IV fixed dose on day −3 before and day +17 after ASCT. The primary endpoint was overall response rate (ORR). Patients aged 18–70 years with MM, of any molecular risk group and with <VGPR status after induction therapy were eligible and received high‐dose melphalan (140–200 mg/m2 IV). Four patients had tandem ASCT with nivolumab. Results: Currently 16 patients were enrolled, 9 males and 7 females with the median age 55 years (range, 45–62). The median follow‐up was 12 months (range, 7–19). Three patients (19%) had light chain MM, three patients (19%) had IgA, ten patients (62%) –IgG MM. All patients received a triple‐agent primary therapy, a median of 6 cycles (range, 4–9). Ten patients had partial response (PR), two patients had stable disease (SD) and four had progressive disease (PD) prior to AHCT. Among these 16 patients, grade 4 toxicity was observed in 1 patient (autoimmune thrombocytopenia after engraftment), grade 3 toxicities ‐ in 3 patients (1 patient with infusion reaction, 1 patient with colitis, 1 patient with neurotoxicity). There were no primary or secondary graft failures, and the median time to neutrophil and platelet engraftment was 12 days (range, 10–17) and 14 days (range, 9–18), respectively. At day+100 after AHCT we evaluated response by serology and bone marrow (BM) study (morphology and flow cytometry), ORR was 56% (9/16): the CR rate was 31% (5/16), 19% (3/16) achieved VGPR, 1 patient (6%) achieved PR. 19% (3/16) maintained PR, 1 patient maintained SD. One of four patients with progressive disease did not achieve response. One of nine patients had relapse. Two patients received second ASCT without nivolumab, one of them achieved CR after second ASCT. At this time all patients are live. Summary/Conclusion: Preliminary results of the addition of nivolumab to ASCT show the relative safety of the therapy. Our pilot study in patients without adequate response before ASCT demonstrate encouraging results of nivolumab combination with ASCT. The efficacy of this combination requires further investigation.