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IntroductionDespite high cure rates with standard treatment, 30% patients with Hodgkin lymphoma develop relapsed or refractory (R/R) disease. Salvage therapy followed by autologous hematopoietic cell transplantation (HCT) is considered standard of care. Brentuximab Vedotin (Bv) in combination with Bendamustine (B) has been tested in the salvage setting with promising results.Materials and MethodologyWe conducted a single centre retrospective chart review of patients who received BBv salvage therapy to determine its activity and safety in patients with R/R classical Hodgkin lymphoma (HL). Between May 2011- December 2019, 179 patients were diagnosed with R/R HL.ResultsThirty patients received BBv [median age: 30 (15-59) years, females (n=15)]. Primary refractory disease in 19 patients (63%), and 26 patients (87%) had advanced stage at treatment. Most patients received BBv after 2 prior lines of therapy [n=16 (53%)]. The median number of cycles of BBv were 3 (1-6). The number of BBv cycles delivered as outpatient was 63%. The most common Grade III/IV hematological adverse event was neutropenia [n=21, (70%)], while grade III/IV non-hematological toxicities included infections in 4 (13%), neuropathy in 4(13%), skin rash in 2 (7%), GI toxicities in 3 (10%) and liver dysfunction in 2 (7%) patients. The ORR and CR rates were 79% and 62%, respectively. Seventeen patients (57%) underwent an autologous HCT and 8 (26%) underwent an Allogeneic HCT (all haploidentical). The median follow up time from BBv administration was 12 months. Six patients died: 2 = disease progression, and 4 = non-relapse causes (Infection and sepsis = 2, GVHD=2). In addition to this, one patient progressed soon after HCT and another patient relapsed 22 months post HCT. Three year Overall survival (OS) and Event free survival (EFS) probability post-BBv treatment was 75% and 58%, respectively. OS and EFS analysis based on response (viz., CMR) to BBv demonstrated that patients in CMR had better survival probability [93% (p=0.0022) 3yr-OS and 72% (p=0.038) 3yr-EFS probability].ConclusionsBBv is an active and well-tolerated salvage treatment for patients with R/R HL, even in refractory and advanced settings. In middle-income settings, cost constraints and access determine patient uptake of this regimen.

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Polatuzumab vedotin is a novel immunotherapy antibody–drug conjugate targeting CD79b. It has been used in relapsed/refractory (R/R) large B-cell lymphomas since its FDA approval in 2019. Presently, this drug is unaffordable or unavailable for patients in Lower–Middle Income Countries (LMIC) like India. This is a retrospective study of adult (> 18 years) patients with R/R large B-cell lymphoma failing two prior lines of therapy, who received Polatuzumab based salvage therapy on a compassionate or named-patient access program. Between May 2019 and April 2022, 10 patients received Polatuzumab vedotin, and 9 were evaluable. The most common regimen used was Polatuzumab-Bendamustine-Rituximab. Out of 43 infusions administered, the adverse event profile was manageable [One grade-2 infusion reaction, 4 patients developed grade 3–4 hematological toxicity and none had grade 3–4 non-hematological toxicities]. Ten infusions were administered in the day care service. After a median of 4.5 cycles (range 1–8), 4 patients achieved CR, 2 had partial response (PR), and 3 had progressive disease (PD). With a median follow up of 491 days (range 8–1048 days), four patients are alive (three in CR and one in PR), three patients have died and three patients were lost to follow up. Early real-world experience from a LMIC setting demonstrates feasibility and a favourable safety profile of Polatuzumab vedotin based approach, along with encouraging response rates in a subset of patients.

INTRODUCTION: Literature on acute myeloid Leukemia (AML) from low and middle income countries (LMIC) like India indicate lower uptake of intensive treatment (29%) and higher induction mortality (25%) (Philip C, BJH 2015). This is attributable to delayed presentation, higher infection burden, multi-drug resistant organism (MDRO) infections, poor nutritional status, access to care, and high costs driven by 'out-of-pocket expenditures', among other reasons. AIM: To determine the clinical profile, cause and costs of care of patients who die during Induction therapy of newly diagnosed AML. METHODOLOGY: This is a retrospective chart review of newly diagnosed AML patients who died during Induction therapy. Induction mortality was defined as death within 60 days from the date of initiation of therapy for newly diagnosed AML. Secondary and therapy related AML were excluded from the study. Demographic and clinical profiling and analyses of the cause of death was undertaken. RESULTs: Between May 2011-Dec 2019, 825 adult patients were registered with newly diagnosed AML. 455 (55.2%) patients discontinued care primarily due to financial constraints, and 370 (44.8%) continued treatment here. Among these (n=370), 275 (74.3%) chose to receive standard or abbreviated intensive therapy (Group A), 58 (15.7%) chose disease control only with continuous less-intensive regimens like hypomethylating agents (Group B) and 37 (10%) chose palliation and best supportive care (Group C). Median age was 55y (20-84) overall, and 39.5y, 67.5y and 69y respectively in groups A, B and C. Females were 59% of the cohort. The overall induction mortality was 13.78% (n=51). Independently, induction mortality was 9.4% (26/275) in Group A, 24.13% (14/58) in Group B and 29.72% (11/37) in Group C, with a yearly trend suggesting a decrease in Group A (Fig 1) in the last 3 years. The most common cause of death was sepsis, 92.1% (n=47), with or without a bleeding episode. Isolated bleeding episodes were accountable for 4% (n=2) of overall deaths, and disease progression in the rest (n=2). Disease burden at presentation (% blasts in peripheral blood and marrow respectively, median values): 40% & 55% in Group A, 47% & 55% Group B, and 60% & 61% in group C. ELN 2017 risk grouping: 16% standard risk (n=8), 51% intermediate risk (n=26) & 33% high risk (n=17). 33% (n=17) had a lung infection at baseline and this was the commonest source of sepsis. Stool and throat surveillance cultures revealed MDRO (carbapenem resistant enterobacteriaceae) in 47% (n=15/32 tests) and 33% (n=7/21 tests) patients, respectively. 74.5% (n=38/51) developed blood culture positive infections during induction therapy. The median number of days to culture positivity was 11 days overall, 13 days in Group A (n=22), 3 in group B (n=13) and 1 day in Group C (n=3). The most common blood culture-detected organism was MDRO Carbapenem resistant Klebsiella (n=12). Imaging detected fungal infection was observed in 47% (n=24). The common antibiotic regimens included meropenem and colistin, with voriconazole being the most common antifungal used. The median ICU stay was 3.5 days (range of 0-24 days) in Group A and 1.5 days (range 0-13) in Group B. The median direct hospital costs in these patients were $6999 in Group A, $7923 in Group B and $2655 in Group C [per-capita GDP of India in 2019: $2099.6]. CONCLUSIONS: The induction mortality in AML varies with age and the intent of treatment. Younger patients undergoing intensive curative therapies have lesser induction mortality. Sepsis is the most common cause of induction deaths, primarily due to a high disease burden and higher infection burden at presentation, and the presence of MDRO bacteremia. Costs of care are very high and contribute to the high drop out rate from curative therapy of newly diagnosed AML. Figure 1 Figure 1. Disclosures Radhakrishnan: Novartis India: Membership on an entity's Board of Directors or advisory committees; NATCO Pharmaceuticals: Research Funding; Janssen India: Honoraria; Intas Pharmaceuticals: Research Funding; Bristol-Myers-Squibb India: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche India: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca India: Honoraria, Speakers Bureau; Aurigene: Speakers Bureau; Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cipla Pharmaceuticals India: Research Funding; Emcure Pharmaceuticals: Research Funding. Garg: Dr Reddys Laboratories: Honoraria, Speakers Bureau. Nair: Intas pharmaceuticals: Honoraria, Speakers Bureau; Fresenius Kabi India: Honoraria; Janssen India: Honoraria, Speakers Bureau; Cipla Pharmaceuticals: Honoraria, Speakers Bureau; Novartis India: Honoraria; Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Mylan pharmaceuticals: Honoraria. Chandy: Intas Pharmaceuticals: Research Funding; Pfizer: Honoraria; Janssen: Honoraria.