Andrew M. Evens1, Ranjana H. Advani2, Irene Helenowski,3 Michelle Fanale4, Sonali M. Smith5, Borko Jovanovic5, Gregory R. Bociek6, Andreas K. Klein7, Jane N. Winter8, Leo I. Gordon8,*, Paul A. Hamlin9,*
1 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 2 Stanford University, Stanford, CA, USA, 3 Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, 4 University of Texas, MD Anderson Cancer Center, Houston, TX, USA, 5 University of Chicago, Chicago, IL, USA, 6 University of Nebraska, Omaha, NE, USA, 7 Division of Hematology/Oncology, Tufts Medical Center, Boston, MA, 8 Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA, 9 Memorial Sloan Kettering Cancer Center, New York, NY, USA
*Authors contributed equally
Purpose: To improve the curability of older patients (pts) with newly diagnosed Hodgkin lymphoma (HL).
Methods: We conducted a multicenter phase 2 study administering brentuximab vedotin (Bv) sequentially before and after standard doxorubicin, vinblastine and dacarbazine (AVD) for untreated HL pts ages ≥60 years (NCT01476410). After 2 ‘lead-in’ doses of single-agent Bv (1.8 mg/kg q3 weeks), pts received 6 cycles of AVD chemotherapy, followed by 4 consolidative doses of Bv in responding pts. Kaplan-Meier estimates were summarized for progression-free survival (PFS) with progression or relapse and death considered as events and they were also summarized for overall survival (OS) with deaths considered as events. Univariable and multivariable Cox proportional hazard regression models accounting for competing risks were also fit to examine variables affecting PFS.
Results: Characteristics included median age 69 years (60–88); 63% male; median ECOG performance status 1; 82% stage III/IV disease; 60% IPS 3–7; median Cumulative Illness Rating Scale-Geriatric (CIRS-G) co-morbidity score 7 (52% grade 3/4); and 12% had baseline loss of instrumental activities of daily living (IADL). Thirty-seven of 48 pts (77%) completed 6 AVD cycles and 35 pts (73%) received at least 1 Bv consolidation. Overall response and complete remission rates after initial Bv lead-in were 18/22 (82%) and 8/22 (36%), respectively; and 40/42 (95%) and 34/42 (90%) respectively, after 6 AVD among 42 response-evaluable pts. For safety, 20 of 48 pts (42%) experienced a grade 3/4 adverse event, most commonly neutropenia (44%); febrile neutropenia and pneumonia (8%); diarrhea (6%); and neuropathy (4%); 33% had grade 2 peripheral neuropathy, the majority which were reversible. By intent-to-treat for all pts with median follow-up of 23 months (2–48 months), the 2-year PFS was 84% with 2-year overall survival of 95% (see Figure). For prognostication, increasing age, increasing CIRS-G co-morbidity score, and loss of IADLs were associated with inferior PFS on univariable and multivariable analyses. Furthermore, the 2-year PFS rates for pts with high CIRS-G co-morbidity score (i.e., ≥10 vs. <10) were 45% vs. 100%, respectively (P<0.0001), and with baseline IADL loss vs. not were 25% vs. 94% (P < 0.0001), respectively (Figure).
Conclusions: Altogether, sequential Bv-AVD was well tolerated, associated with robust outcomes, and geriatric-based measures were strongly associated with patient survival.
Copyright © 2018 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.