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
Author(s): ,
Olga Pirogova
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Hematology, Oncology and Transplantation,First Pavlov State Medical University,St. Peterburg,Russian Federation
,
Elena Darskaya
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Hematology, Oncology and Transplantation,First Pavlov State Medical University,St. Peterburg,Russian Federation
,
Valentina Porunova
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Hematology, Oncology and Transplantation,First Pavlov State Medical University,St. Peterburg,Russian Federation
,
Olga Kudyasheva
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Hematology, Oncology and Transplantation,First Pavlov State Medical University,St. Peterburg,Russian Federation
,
Elena Babenko
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Hematology, Oncology and Transplantation,First Pavlov State Medical University,St. Peterburg,Russian Federation
,
Natalia Mikhailova
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Hematology, Oncology and Transplantation,First Pavlov State Medical University,St. Peterburg,Russian Federation
Boris Afanasyev
Affiliations:
R.M. Gorbacheva Memorial Institute of Children Hematology, Oncology and Transplantation,First Pavlov State Medical University,St. Peterburg,Russian Federation
EHA Library. PIROGOVA O. Jun 15, 2019; 267013; PS1396
Mrs. Olga PIROGOVA
Mrs. Olga PIROGOVA
Contributions
Abstract

Abstract: PS1396

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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

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.

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.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Autologous hematopoietic stem cell transplantation, Multiple myeloma

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