ISHL13 Abstract T106

Pembrolizumab maintenance instead of autologous hematopoietic cell transplantation for patients with relapsed or refractory Hodgkin lymphoma in complete response after pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin

Introduction: In our phase II study evaluating pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin (P-GVD) followed by high dose therapy and autologous hematopoietic cell transplantation (AHCT) (Moskowitz, et al. JCO 2021) for relapsed or refractory (RR) Hodgkin lymphoma (HL), 95% of pts achieved complete response (CR) and 96% are progression-free at 30 months. Building upon these results, we explored whether pts achieving CR after P-GVD could avoid AHCT.

Methods: After 1-line of therapy, RR HL pts received 4 cycles of P-GVD and those who achieved CR proceeded to 13 cycles of pembrolizumab maintenance (PM). Primary endpoint was 2-year progression free survival (PFS) after PM.

Results: Among 40 patients enrolled, median age was 36 (range 19-76), 18 (45%) were male, 17 (43%) had primary refractory disease, 18 (45%) had extranodal disease, 16 (40%) had stage IV disease, and 7 (18%) had B symptoms at enrollment. All pts responded to P-GVD, including 36 (90%) with CR and 4 (10%) with PR. Of 36 pts with CR, 5 elected to proceed to AHCT, 4 were referred to AHCT by treating physician due to treatment-related toxicity (1 pt with G4 immune thrombocytopenia and G2 pneumonitis; 1 with G1 pneumonitis, 1 with G2 rash, 1 with G3 PJP pneumonia), 2 elected to come off study and receive no further treatment. Among 25 patients who proceeded to PM, 11 events occurred, including 1 death from pneumonitis (after 4 cycles of P-GVD) and 10 progressions. After a median follow-up of 26 mos for PM pts, 2-year PFS was 56% (95% CI 38-82) (Figure 1A). Stage IV disease at enrollment had a trend towards higher risk for progression (PFS 36% vs 65%, p=0.07). Nine of the 10 pts who progressed successfully proceeded with AHCT and remain in remission after a median of 12.7 months (range: 3.8-24.4) post-transplant (Figure 1B). One patient with progression was not eligible for transplant due to comorbidities and is receiving palliative treatment with pembrolizumab plus gemcitabine.

Conclusion: After a median follow-up of 26 mos, 56% of pts with RR HL treated with P-GVD followed by PM are progression free. Furthermore, pts who relapse during or after PM can be salvaged with third-line therapy and AHCT. Patients with stage IV disease are more likely to need ASCT. A randomized study evaluating AHCT versus PM for patients with RR stage I-III HL who achieve CR to P-GVD is underway.