“Big Boom” Radiation Treatment (RT) of 4 Gy Single Fraction: Is It an Acceptable Alternative to “Boom Boom” Radiation Treatment 2 Gyx2 Fractions for Non-Hodgkin Lymphomas (NHL)?

Purpose/Objective(s): RT plays an important role in the treatment of NHL. Early in the COVID-19 pandemic, in order to decrease patient and staff exposure to potential infection, the International Lymphoma Radiation Oncology Group [ILROG] published emergency guidelines to support hypofractionation across multiple dose regimens. For NHL, ILROG recommended substitution of the familiar 2 Gy x2 regimen with a 4 Gy x1 alternative. This preliminary report describes our center's experience with a regimen of a single dose of 4 Gy (“Big Boom”). Materials/Methods: We present our initial findings of patients treated with 4 Gy x1 between March 30, 2020 through November 30, 2020 (n = 40 lesions;36 patients). We utilized Lugano PET criteria and clinical assessments to determine patient outcomes. Outcomes included initial clinical/radiographic response and acute toxicities. Patients were treated with either a definitive (curative) or a palliative intent (to relieve symptoms and not necessarily to achieve long-term disease control). Results: Table 1 summarizes the patient and treatment characteristics. 29 patients (72%) were treated with a definitive intent, and 11 (28%) with a palliative intent. Median time to initial assessment for all sites was 2.2 months (range: 0.6-4.4), with overall median follow up time of 3.8 months (range: 1.0-7.3). The overall initial response rate was 85% for all sites, with 59% achieving complete response (CR) and 26% achieving a partial response (PR) (n = 39 lesion sites;35 patients – 1 patient deceased shortly after RT [unrelated to radiation]). 4 initial partial response/no response (PR/NR) sites later became CR with either additional full dose RT (2 Gyx12) or no other treatments. The median follow-up time for those 4 lesions sites was 4.2 months (range: 2.3-9.2). 9 patients reported grade 1 toxicity, and none had grade 2+ toxicity. Conclusion: Given the initial high response rate and the ease of using a “one and done” treatment method, we propose that the early response rates of using a 4 Gyx1 regimen are similar to that of 4 Gy in 2 fractions. Longer term follow-up is required to confirm the durability of these results. As we continue to accrue and evaluate, data will be updated at the time of the meeting and potentially joined with other centers participating in the comprehensive ILROG-COVID guidelines research effort.

Efficacy and Toxicity of Alternative Radiation Treatment Schemes for Patients With Hematologic Malignancies: A Collaborative ILROG COVID Era Report

Purpose/Objective(s): The COVID19 pandemic required radiation oncologists (ROs) to consider shorter treatment courses to minimize patient and staff exposure and conserve healthcare resources. Hematologic ROs adopted hypofractionated radiation therapy (hRT) regimens according to guidelines published by the International Lymphoma Radiation Oncology Group (ILROG). We report for the first time the preliminary efficacy and toxicity of these novel hypofractionated regimens in the treatment of hematologic malignancies. Materials/Methods: We conducted a multicenter, multinational retrospective study under the direction of the ILROG. All patients receiving hRT according to ILROG guidelines from 1/1/2020 to 8/31/2020 were included. Patient and treatment details were abstracted from separate institutional databases. Toxicity was graded using CTCAE v5.0. Results: Ninety-three patients from 4 institutions treated with 114 RT courses were included. Patient and treatment details are displayed in Table 1. Median follow up for the cohort was 179 days, and 77 patients (82%) were alive at last follow up. Maximal toxicity experienced by patients included Grade 1 (n = 16), Grade 2 (n = 1) and Grade 3 (n = 1) toxicities. Of 80 sites with response assessment within the RT field, 69% of patients achieved a complete response (n = 55), 20% partial response (n = 16), 9% stable disease (n = 7), and 2% progressive disease (n = 2). No COVID19 infections during or after RT have been documented in this patient cohort. Conclusion: HRT according to ILROG guidelines resulted in low rates of acute toxicity and reasonable short-term treatment efficacy. Longer follow up and comparison with control groups is needed to draw more definitive conclusions and will be presented at the Annual Meeting.

Phase II Study of Pembrolizumab Plus GVD As Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma

Introduction: 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). No one standard SLT exists and options include regimens containing platinum, gemcitabine, and more recently brentuximab vedotin (BV). Complete response rates associated with these regimens range from 50-70%. Due to the increasing use of BV in the front-line setting, development of SLT regimens that are both highly effective and BV-sparing are needed. Programmed death-1 (PD-1) inhibitors are highly active in RR cHL and have the potential to enhance the efficacy of standard chemotherapy. Here we report the results of our phase II study evaluating a novel anti-PD-1-based regimen, pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembrolizumab-GVD), as SLT for RR cHL. Methods: Transplant eligible patients (pts) with RR cHL following failure of 1-line of therapy were eligible. Treatment consisted of 2 to 4 cycles of pembrolizumab (200mg IV, day 1), gemcitabine (1000mg/m2 IV, days 1 and 8), vinorelbine (20mg/m2 IV, days 1 and 8) and liposomal doxorubicin (15mg/m2, days 1 and 8), given on 21-day cycles. Pts who achieved CR by PET (Deauville ≤3) after 2 or 4 cycles proceeded to HDT/AHCT. HDT/AHCT was carried out according to institutional standards and BV maintenance was allowed following HDT/AHCT. The primary endpoint was CR rate after 2 or 4 cycles of pembrolizumab-GVD. Enrollment occurred according to a Simon 2-stage design with sample size based upon a projected CR rate of 70%. In stage 1, 23 pts enrolled and 12 or more CRs were required to proceed to stage II;in stage II, an additional 16 pts enrolled. Out of a total of 39 pts, 24 CRs were required to declare this regimen promising. Results: Among 39 patients enrolled, 37 are evaluable for toxicity (2 pts have not yet started treatment) and 34 are evaluable for response (4 pts too early, 1 pt found to have composite lymphoma after enrollment). Of 37 treated pts, median age is 36 (range 21-71), 43% are male, 23 (62%) had advanced stage disease, and 15 (41%) had primary refractory disease. With regard to RR cHL risk factors (B-symptoms, extranodal disease, and relapse/refractory disease within 1 year of initial treatment), 4(11%) had no risk factors (RFs), 21 (57%) had 1 RF, 9 (24%) had 2 RFs, and 3 (8%) had all 3 RFs. Treatment was well tolerated with most adverse events being grade 1 or 2 (see figure 1). Grade 3 AEs included rash (n=1), elevated AST/ALT (n=3), oral mucositis (n=2), and neutropenia (n=3). Figure 2 shows the outcome for all 37 treated pts. Among 34 evaluable pts, 31 (91%) achieved CR after 2 cycles and 3 achieved partial response. An additional 1 pt achieved CR after 4 cycles of pembrolizumab-GVD, therefore in total, 32 of 34 (94%) achieved CR following pembrolizumab-GVD. 4 pts with CR after 2 cycles received an additional 2 cycles of pembrolizumab-GVD in order to delay HDT/AHCT during the height of the COVID-19 pandemic (n=3) or due to refusing HDT/ASCT (n=1). To date, 32 have undergone HDT/AHCT following 2 (n=27) or 4 (n=5) cycles of treatment. 1 pt is awaiting HDT/AHCT;1 pt refused HDT/ASCT and received pembrolizumab maintenance instead. 2 pts received involved site radiation therapy to initial area of relapsed disease prior to planned HDT/AHCT and 10 pts received post-HDT/ASCT maintenance with BV. Median follow-up post-HDT/AHCT is 9 mos (range 0.03-20.9 mos) and all pts remain in remission to date. Conclusion: Second-line therapy with pembrolizumab-GVD is a highly effective and well-tolerated regimen that can efficiently bridge pts with RR cHL to HDT/AHCT. Updated results including all 39 enrolled pts will be presented at the meeting. Given the high CR rate observed with pembrolizumab-GVD, an expansion cohort evaluating 8 cycles of pembrolizumab maintenance (instead of HDT/AHCT) for patients who achieve CR af er 4 cycles of pembrolizumab-GVD is planned. [Formula presented] Disclosures: Moskowitz: Merck: Consultancy;Incyte: Research Funding;Miragen Therapeutics: Consultancy;Seattle Genetics: Consultancy;Imbrium Therapeutics, L.P.: Consultancy;Merck: Research Funding;Seattle Genetics: Research Funding;Bristol-Myers Squibb: Research Funding. Shah: Amgen Inc.: Research Funding;Janssen: Research Funding. Kumar: AbbVie: Research Funding;Celgene: Honoraria, Other: Honoraria for Advisory Board;Seattle Genetics: Research Funding;Astra Zeneca: Honoraria, Other: Honoraria for Advisory Board;Celgene: Research Funding;Kite Pharmaceuticals: Honoraria, Other: Honoraria for Advisory Board;Adaptive Biotechnologies,: Research Funding;Pharmacyclics: Research Funding. Lahoud: MorphoSys: Other: Advisory Board. Batlevi: Life Sci, GLG, Juno/Celgene, Seattle Genetics, Kite: Consultancy;Janssen, Novartis, Epizyme, Xynomics, Bayer, Autolus, Roche/Genentech: Research Funding. Hamlin: J&J Pharmaceuticals: Research Funding;Portola: Research Funding;Incyte: Research Funding;Portola Pharmaceutics: Consultancy;Juno Therapeutics: Consultancy;Karyopharm: Consultancy;Celgene: Consultancy;Molecular Templates: Research Funding. Straus: Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees;Imedex, Inc.: Speakers Bureau;Targeted Oncology: Consultancy, Speakers Bureau;NY Lymphoma Rounds: Consultancy;Takeda Pharmaceuticals: Research Funding, Speakers Bureau;OncLive: Speakers Bureau;Elsevier: Membership on an entity's Board of Directors or advisory committees, Other: CME writer;ASH: Other: Conference in December 2019 on HL to other physicians during ASH;Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Horwitz: ASTEX: Consultancy;Verastem: Consultancy, Research Funding;Myeloid Therapeutics: Consultancy;Miragen: Consultancy;Kura Oncology: Consultancy;Janssen: Consultancy;GlaxoSmithKline: Consultancy;Daiichi Sankyo: Research Funding;C4 Therapeutics: Consultancy;Affirmed: Consultancy;Vividion Therapeutics: Consultancy;Beigene: Consultancy;Portola: Consultancy, Research Funding;Mundipharma: Consultancy;Innate Pharma: Consultancy;Corvus: Consultancy;Trillium: Consultancy, Research Funding;Seattle Genetics: Consultancy, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Kyowa Hakka Kirin: Consultancy, Research Funding;Infinity/Verastem: Research Funding;Forty Seven: Consultancy, Research Funding;Celgene: Consultancy, Research Funding;Aileron: Consultancy, Research Funding;ADCT Therapeutics: Consultancy, Research Funding. Falchi: Genmab: Research Funding;Roche: Research Funding. Joffe: Epizyme: Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Noy: Pharmacyclics: Research Funding;Pharmacyclics: Consultancy;Janssen: Consultancy;Rafael Pharma: Research Funding;NIH: Research Funding;Morphosys: Consultancy;Medscape: Consultancy;Targeted Oncology: Consultancy. Matasar: Teva: Consultancy;Genentech, Inc.: Consultancy, Honoraria, Research Funding;Merck: Consultancy;Bayer: Consultancy, Honoraria, Research Funding;Juno Therapeutics: Consultancy;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;GlaxoSmithKline: Honoraria, Research Funding;IGM Biosciences: Research Funding;Janssen: Honoraria, Research Funding;Pharmacyclics: Honoraria, Research Funding;Immunovaccine Technologies: Honoraria, Research Funding;Rocket Medical: Consultancy, Research Funding;Takeda: Consultancy, Honoraria;Daiichi Sankyo: Consultancy;Seattle Genetics: Consultancy, Honoraria, Research Funding. Vardhana: Other: Other: SAV has received honoraria from Agios Pharmaceuticals and Rheos Pharmaceuticals, is an advisor for Immunai and has consulted for ADC Therapeutics. von Keudell: Genentech: Research Funding;Bayer: Research Funding;Pharmacyclics: Research Funding. Zelenetz: Novartis: Consultancy;Janssen: Consultancy;Celge e: Consultancy;Amgen: Consultancy;Adaptive Biotechnology: Consultancy;BeiGene: Membership on an entity's Board of Directors or advisory committees;Roche: Research Funding;Gilead: Research Funding;Genentech/Roche: Consultancy;Gilead: Consultancy;Sandoz: Research Funding;Celgene: Research Funding;MEI Pharma: Research Funding;MorphoSys: Research Funding. OffLabel Disclosure: Pembrolizumab as second-line therapy for Hodgkin lymphoma