T099: High efficacy and durability of second-line therapy with pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin in the phase II study for relapsed and refractory Hodgkin lymphoma

Figure 1: Progression-free survival for patients enrolled onto part I of the phase II study evaluating P-GVD followed by consideration for HDT/AHCT. 36 pts underwent HDT/AHCT. 2 pts declined transplant and were censored after 2 and 3 months. Introduction/Methods: The standard approach for relapsed or refractory (RR) classical Hodgkin lymphoma (cHL) following front-line treatment failure is second line therapy (SLT) aimed to achieve complete response (CR), followed by consolidation with high dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). We previously reported results from part I of a phase II study evaluating SLT with pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin (P-GVD) followed by HDT/AHCT (Moskowitz, et al. JCO 2021). We are now enrolling onto part II in which patients with CR after 4 cycles of P-GVD proceed to 13 cycles of pembrolizumab maintenance rather than HDT/AHCT. We present here extended follow-up from part I as well as updated efficacy and toxicity data for P-GVD from parts I (n=39) and II (n=33). Results: Part I included 39 pts evaluable for toxicity and 38 evaluable for efficacy. Among 38 evaluable pts, CR and overall response rates (ORR) were 95% and 100%. 36 pts proceeded to HDT/AHCT, of whom 13 (36%) received post-transplant brentuximab vedotin (BV) (n=12) or BV plus nivolumab (bv/nivo) (n=1) maintenance. After a median follow-up of 30 (range: 2–43) months, 1 pt experienced progression 23 months after transplant. The estimated 30-month progression-free survival (PFS) is 96% (Figure 1). To date, all 33 pts enrolled to part II are evaluable for toxicity and 30 pts for response to P-GVD. Among those, 27 (90%) achieved CR (including 2 with PET-avid findings that were biopsy negative) and 3 (10%) achieved partial response. Among 68 pts evaluable for response from parts I and II, CR and ORR rates were 92.6% and 100%. Among 72 pts evaluable for toxicity, grade 4 or 5 events included grade 4 sepsis (n=1) and grade 5 pneumonitis (n=1, occurred after 4 cycles of P-GVD, pt enrolled on part II). Grade 3 events occurring in >1 pt included neutropenia (n=9, 12.5%), elevated AST/ALT (n=7, 10%), mucositis (n=5, 7%), anemia (n=4, 5%), lung infection (n=2, 3%), and rash (n=2, 3%). Conclusion: Second-line therapy with P-GVD is highly effective and efficiently bridges pts with RR cHL to HDT/AHCT. With extended follow-up for transplanted pts, remissions remain durable with estimated 30-month PFS of 96%. Among 68 evaluable pts enrolled onto parts I and II, CR rate remains high at 92.6%. Enrollment onto part II, which is assessing the role of pembrolizumab maintenance as an alternative to HDT/AHCT for patients in CR, is ongoing.