Relapsed/refractory patients,   Patients eligible for transplant

EBMT 2018 | Haploidentical transplantation in patients with high-risk or multiply relapsed MM

The MM Hub were delighted to attend the 44th Annual Meeting of the European Society for Blood and Marrow Transplantation held in Lisbon, Portugal, from 18–21 March 2018. On Monday 19 March 2018 the oral abstract session 4 was held. The session was moderated by Catarina Geraldes, from the Department of Clinical Hematology, University of Coimbra, Portugal and Tamás Masszi, the Department of Internal Medicine, Semmelweis University, Budapest, Hungary.

The second talk in this session was  delivered by Firoozeh Sahebi, from City of Hope, Duarte, US and  entitled: The outcome of haploidentical transplantation in patients with relapsed multiple myeloma. An EBMT/CIBMTR report. This was a retrospective analysis to examine the outcome of patients with multiple myeloma (MM) that had haploidentical stem cell transplantation, using data from the European Society for Blood and Marrow transplantation (EBMT) and Center for International Blood and Marrow Transplant Research (CIBMTR) registries.

 Key Findings:
  • N = 96 patients (pts) that underwent transplant from 2008–2016
  • Median age = 54.9 years (36.6­­­­­­–73.3)
  • International staging system (ISS) stage I-II = 43 pts; ISS stage III = 37 pts; missing = 16
  • Subtype (pts): IgG = 41; IgA = 15; light chain = 34; others = 4; missing = 2
  • Number of prior autologous transplants: 1 = 66 pts; >1 = 30 pts
  • Disease status: complete response (CR)/sCR/very good partial response (VGPR) = 36 pts, partial response (PR) = 30 pts, stable disease (SD) = 13 pts, PD/relapse = 17 pts
  • Time from diagnosis: >24 months = 79 pts; 18–24 months = 8 pts; <18 months = 9 pts
  • Recipient/donor gender match: M/M = 31 pts; M/F donor = 31 pts; F/M donor = 17 pts; F/F = 16 pts
  • Stem cell (SC) source: bone marrow (BM) = 33 pts; peripheral blood (PB) = 62 pts; missing = 1 pt
  • Conditioning: myloablative = 18 with total body irradiation (TBI) = 5 pts; non TBI = 13 pts; reduced intensity with TBI = 52 pts; without TBI = 25 pts; missing = 1 pt
  • Graft versus host disease (GvHD) prophylaxis: post-transplant cyclophosphamide (post-Cy) = 73 pts; no post-Cy = 17 pts; anti-thymocyte globulin (ATG) alone = 11 pts; No ATG = 80 pts and missing = 2 pts
  • Median follow-up = 19.9 months (9.3–39.1)
  • Engraftment absolute neutrophil count (ANC) > 500 by day 28 = > 97% (93–100) of pts
  • Engraftment for platelets by day 60 = 75% (66–84) of pts
  • Overall survival (OS) at 2-years = 48% (36–59%)
    • With cumulative risk of relapse at 2-years = 56% (45–67)
    • Non Relapse Mortality (NRM) at 2-years = 26% (17–36)
  • Progression free survival (PFS) at 2-years = 17% (6–26)
  • Incidence of acute GvHD (aGvHD):
    • Grade II–IV = 39% (28–49)
    • Grade III–IV = 12% (5–19)
  • Incidence of chronic GvHD (cGvHD) at 2-years = 46% (34–59)
  • Stem cells from the bone marrow has a positive impact on OS in comparison to SC from peripheral blood (P = 0.001)
  • Univariate analysis:
    • Higher relapse rate with the use of ATG/Campath (P = 0.001) and TBI + Cy-based regimens (P local trend (LT) = 0.001)
    • Lower OS with the use of ATG (P = 0.01) and TBI + other conditioning (P = 0.01)
    • Higher NRM with the use of ATG (P = 0.012), or TBI based regimens (P = 0.005)
    • No impact of cytomegalovirus (CMV) status on NRM or GvHD
    • Higher OS for patients where the stem cell source was from the BM

These results indicate the feasibility of haploidentical transplantation in high-risk or multiply relapsed MM patients, with a median 2-year OS of 48%. It was also observed that 21% of the patients had an acceptable NRM at 1 year and 26% of the patients at 2 years. The speaker suggested that haplo-SCT should be considered for further investigation of immune therapies, to induce a myeloma specific response.

References
  1. Sahebi F. et al. The outcome of haploidentical transplantation in patients with relapsed multiple myeloma. An EBMT/CIBMTR report. #Abstract OS4-2. 44th Annual Meeting of the European Society for Blood and Marrow Transplantation, Lisbon, Portugal.