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
Authors: Moskowitz Alison , Shah Gunjan L. , Ganesan Nivetha , Chang Tiffany , Drill Esther , Davey Theresa , Hancock Helen , Munayirji Brittney , Douglas Monifa , Santarosa Alayna M. , Casper Ellie , Galasso Natasha , Subzwari Sarima , Jihad Marwah , Boardman Alexander P. , Caron Philip , David Kevin A. , Epstein-Peterson Zachary D. , Falchi Lorenzo , Ghione Paola , Hamlin Paul A. , Horwitz Steven , Intlekofer Andrew M. , Johnson William T. , Kumar Anita , Lue Jennifer Kimberly , Luttwak Efrat , Noy Ariela , Owens Colette , Palomba Maria Lia , Salles Gilles , Steiner Raphael , Stuver Robert , Torka Pallawi , Vardhana Santosha A. , Zelenetz Andrew D. , Yahalom Joachim , Dogan Ahmet , Schoder Heiko , Moskowitz Craig H. 
Published: December 2024

Introduction: The standard approach for relapsed or refractory (RR) classical Hodgkin lymphoma (HL) 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 our phase II study evaluating SLT with pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin (P-GVD) followed by HDT/AHCT (Moskowitz, et al. JCO 2021) in which 95% of patients achieved CR and 96% are progression-free at 30 months. Building upon the excellent results observed with P-GVD, we next explored whether patients achieving CR after P-GVD could avoid HDT/AHCT.

Methods: Part II of the P-GVD study enrolled patients with RR HL following 1 line of therapy. Patients received 4 cycles of P-GVD and those who achieved CR proceeded to 13 cycles of pembrolizumab maintenance (200mg IV every 21 days). The primary endpoint was 2-year progression free survival (PFS) after start of maintenance. Our hypothesis was that this treatment would lead to a 2-year PFS of 75% but no less than 50%, thus we aimed to initiate pembrolizumab maintenance in 23 patients who achieved CR after P-GVD to ensure a power of 80% and significance of 0.05.

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, and 1 died from pneumonitis following 4 cycles of P-GVD before proceeding to maintenance. Among 24 pts who proceeded to maintenance, 10 experienced progression of HL either during pembrolizumab maintenance (n=3), 3-6 months after completion of pembrolizumab maintenance (n=4), or &gt; 10 months from completion of pembrolizumab maintenance (n=3).

After a median follow-up of 23.4 mos, 2-year PFS was 51% (95% CI 33-80). Stage IV disease at enrollment was significant for higher risk of progression (PFS 18% vs 69%, p=0.03). 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. 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 23.4 mos after maintenance, 51% of pts with RR HL treated with P-GVD followed by maintenance were progression free. Furthermore, pts who relapsed during or after maintenance were salvaged with third-line therapy and AHCT. Patients with stage IV disease are more likely to need AHCT. A randomized study evaluating AHCT versus pembrolizumab maintenance for patients with RR stage I-III HL who achieve CR to P-GVD is underway.