PB2348 IMMUNE RECONSTITUION OF ΓΔT CELLS AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA – IMPACT OF REFRACTORINESS/RELAPSE AND PREVIOUS THERAPEUTICS ON RECOVERY
Authors: Roque A. , Silva I. , Afonso M. C. , Cortesão E. , Espadana A. I. , Sarmento‐Ribeiro A. B. , Geraldes C. , Paiva A. , Ribeiro M. L. 
Published: June 2019

Background:

γδT cells are a minor circulant effector/cytotoxic population involved in immune surveillance, with evidence supporting their anti‐multiple myeloma (MM) role. Although lymphocyte recover after autologous hematopoietic stem cell transplantation (aHSCT) has been extensively studied, there are limited data about γδT cells, with no information on the impact of previous therapeutic in its recovery.

Aims:

To evaluate γδT cells recovery in MM patients(pts), its impact in posttransplant recovery and the effect of previous treatment/response in γδT subsets reconstitution.

Methods:

We prospectively analysed 44 MM pts submitted to aHSCT (2016‐2018), previously to conditioning with melphalan 200 mg/m2 (Dc) and at 30 (D30), 60 (D60), and 100 (D100) days after aHSCT. The proportion (%) of γδT cells, performed by flow cytometry based on the expression of CD3/CD45/Vδ1/Vδ2/Vγ9/CD27, indicated the proportion of these cells among all T cells. Pts were divided into 3 groups: those who receive just 1‐line therapy previous aHSCT (NEW) and those who receive more than 1 line due to primary refractory disease (REFAC) or relapse after response (RECID), according to IMWG criteria. Toxicities were graded according to CTCAEv4.03.

Results:

Median age was 63 years (40‐69), with 64.0% of males, 27.3% ISS III. Median of previous therapeutic lines was 1(1‐4) – all pts had received bortezomib, 27.3% lenalidomide, 18.8% thalidomide, 9.1% daratumumab, and 4.6% pomalidomide; 36.4% received ≥1 novel anti‐MM agent.

Median time diagnosis‐aHSCT was 11.1 months(5.3‐112.1) – 68.2%(n = 30) NEW, 16.6%(n = 6) REFAC and 18.2% (n = 8) RECID. The median number of previous lines was higher in REFAC vs RECID (2vs2; p = 0.015). There were no other characteristics differences at diagnosis between the 3 groups. There was no significant difference between NEW vs REFAC vs RECID in achieving at least very good partial response (VGPR) or higher previous to aHSCT (p = 0.224) or at D100 pos‐aHSCT (p = 0.905).

RECID group presented a higher % of Vδ1 + γ9 + T cells (vs REFAC)(p = 0.007) and a lower of Vδ2 + γ9 + T(vs REFAC and NEW)(p = 0.060 and p = 0.027, respectively) at D100. There were no other differences between the 3 groups.

Time to neutrophils >0.5 × 109/L (TTN) was higher in RECID group (vs NEW and REFAC) (p = 0.003 and p = 0.015, respectively). A higher TTN was positively correlated with a higher %Vγ9 + T (Coef. 21,4;p = 0.012), Vδ1 + γ9 + T(Coef 17.7;p = 0.007) and Vδ1 + γ9 + CD27 + T(Coef 35.9;p = 0.008)(D60), even after adjusting for the study group. Time to platelets >20 × 109/L (TTP) was higher in RECID vs NEW (p = 0.005). REFAC group needed more platelet transfusion vs NEW (p = 0.011). A higher % Vγ9 + T(D60) was associated with higher platelet transfusion requirement (Coef 7.4;p = 0.016), even after group adjusting. Despite a positive association between TTP and Vγ9 + T (D60)(Coef 20.8; p = 0.019), there was a loss significance after adjusting for group (p = NS).

For a median follow up of 17.6 months, progression free survival (PFS) at 1‐year post‐aHSCT was lower in REFAC, although not significant(p = 0.276). None subset of Vγδ + T cells presented impact in PFS.

Summary/Conclusion:

Our results, although conditioned by a small sample size and a short follow‐up, show a higher % of Vδ1 + Vγ9 + T and lower Vδ2 + Vγ9 + T cells in patients’ group RECID at D100. Furthermore, our data suggests that γδT subsets (particularly Vδ1+, Vδ1 + Vγ9+ and Vγ9+) seem to have a role in delaying haematological recovery, mainly in megakaryocytic line. Further studies are needed to evaluate the relationship between these T cells subpopulations and the response to therapeutics/aHSCT, as well as the benefit of its modulation.