Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Hodgkin Lymphoma Clinical Trials
Hematology Disease Topics & Pathways:
Hodgkin Lymphoma, Clinical Trials, Lymphomas, Clinical Research, Clinically Relevant, Diseases, Lymphoid Malignancies
Methods: Adult pts with RR HL who had failed at least 1 prior line of therapy and were transplant-ineligible were enrolled to receive IV pembrolizumab and oral vorinostat in 21-day cycles. Prior anti-PD1 exposure was allowed. Anti-PD1 refractory was defined as stable disease (SD) or progressive disease (PD) as best response or PD during anti-PD1 therapy after objective response. Pts were treated in a dose-escalation cohort with 2 dose levels (DL) using a Rolling 6 design and then onto an expansion cohort with treatment at the recommended phase 2 dose (RP2D). In DL1, vorinostat was administered orally at 100mg BID on days 1-5 and 8-12 and in DL2, vorinostat was administered at 200mg BID on days 1-5 and 8-12. Pembrolizumab dose was 200mg IV every 3 weeks in all DLs. Treatment could continue for a maximum of 2 years. The primary endpoint was safety and determination of the RP2D. Responses were assessed by investigators using PET-CT according to the 2014 Lugano Classification.
Results: 32 HL pts were enrolled, including 2 at DL1 and 30 at DL2 (RP2D). At baseline, 69% were male, 72% were Caucasian, the median age was 35 years (range 18-79), and 75% had stage III-IV disease. The median number of prior therapies was 4 (range 2-12), 94% had prior brentuximab vedotin (BV), 66% were BV refractory, 78% had prior PD1 blockade and 56% were PD1 refractory. Baseline characteristics are shown in Table 1.
The median number of cycles was 8.5 (range 1-36). The most common adverse events (AEs, any grade, Gr) were hypertension (72%), fatigue (63%), hyponatremia (63%), nausea (63%), diarrhea (47%), thrombocytopenia (44%), anemia (41%). The most common Gr 3+ AEs included hypertension (9%), neutropenia (6%), thrombocytopenia (6%), hypophosphatemia (6%), and lymphopenia (6%). Immune-related AEs included 4 pts with Gr 1-2 thyroiditis, 1 pt with Gr 1 rash, and 1 pt with Gr 3 esophagitis/duodenitis. 1 pt had vorinostat dose reduction for neutropenia. 20/32 pts discontinued treatment; treatment was discontinued for disease progression in 11 pts, stem cell transplant in 6 pts, patient preference in 2 pts, and completion of 2 years of therapy in 1 pt.
Among 30 evaluable pts (2 too early), the best overall response rate (ORR) was 73% and the CR rate was 33% (Table 2). Among anti-PD1 naïve/sensitive pts (n=14), the ORR and CR rate were 93% and 64%. Among pts who were refractory to prior PD1 blockade (n=18), the ORR and CR rate were 56% and 6%. 10 evaluable anti-PD1 refractory pts had PD1 blockade as their most recent therapy (median 35 days between PD and study treatment start), and 6 (60%) had an objective response to pembro/vorinostat (all partial responses). The median follow-up time in 28 surviving pts was 18 months (mo, range 1-41). The median duration of response, progression-free survival (PFS), and overall survival (OS) in all RR HL patients were 14 mo, 14.9 mo, and not reached. The 1-year PFS and OS were 52% and 93%.
Conclusions: Pembrolizumab and vorinostat was tolerable and produced a high ORR and CR rate in pts with anti-PD1 naïve/sensitive RR HL. A majority of pts with anti-PD1 refractory RR HL had objective responses, including pts who had progressed while receiving PD1 blockade as their most recent therapy.
Disclosures: Herrera: Bristol Myers Squibb: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Kite, a Gilead Company: Research Funding; Tubulis: Consultancy; Gilead Sciences: Research Funding; Takeda: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Seagen: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy, Research Funding. Budde: Kite Pharma: Consultancy; Genentech: Consultancy, Research Funding; AstraZeneca: Research Funding. Nikolaenko: Rafael Pharmaceuticals: Research Funding; Pfizer: Research Funding. Chen: AstraZeneca: Current Employment; Autolus: Ended employment in the past 24 months. Forman: Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Allogene: Consultancy; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company. Popplewell: Pfizer: Other: Travel; Hoffman La Roche: Other: Food; Novartis: Other: Travel. Kwak: Pepromene Bio, Inc.: Consultancy, Current equity holder in publicly-traded company. Mei: TG Therapeutics: Research Funding; Epizyme: Research Funding; EUSA: Honoraria; Janssen: Honoraria; Morphosys: Research Funding; BMS: Research Funding; Beigene: Research Funding.
OffLabel Disclosure: Vorinostat is not FDA-approved for use in patients with Hodgkin lymphoma
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