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35 citation(s) found for "Major, Ajay".

A real-world analysis of safety and outcomes with first line nivolumab in combination with doxorubicin, vinblastine, and dacarbazine (NAVD) in patients with classic Hodgkin lymphoma (cHL) – a multicenter cohort study
Bock, Allison M. , Thiruvengadam, Swetha, Sano, Dahlia , Sekaran, Kanithra , Vaughn, John, Sharp, John , Patel, Vrutti , Araújo, Ney Soares de, Mynam, Ritwick , Smilnak, Gordon , Palmeri, Marisa, Abhyankar, Anuja , Gerber, Drew, Geethakumari, Praveen Ramakrishnan , Baek, Grace , Shanmugasundaram, Krithika , Feldman, Tatyana , Svoboda, Jakub , Karimi, Yasmin , Herrera, Alex F. , Torka, Pallawi , Karimi, Yasmin H , Luttwak, Efrat , Назаренко, Елена Борисовна , Xu, Yizhe , Thiruvengadam, Swetha, Vaughn, John, Reef, Daniel K. , Major, Ajay , Araujo, Nicole, Falade, Ayo , Iqbal, Madiha , Di, Mengyang , Hu, Boyu , Durani, Urshila , Cherng, Hua‐Jay J. , Niu, Alex , Rhodes, Joanna , Pophali, Priyanka A. , Voorhees, Timothy , Grover, Natalie S. , Diefenbach, Catherine , Karmali, Reem , Epperla, Narendranath

Mayo Clinic

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 1841-1841

10.1182/blood-2025-1841 Get It

Abstract Introduction: NAVD has become a standard-of-care for frontline (1L) treatment (tx) of advanced stage cHL, based on the results of the S1826 study. S1826 demonstrated a 1-year progression free survival (PFS) of 94% for NAVD compared to 86% for brentuximab vedotin-AVD, which remained durable at 2 years (Herrera et al, NEJM 2024). Adverse events (AEs) and efficacy have not been reported in patients (pts) treated with NAVD outside of a clinical trial. Hence, we sought to evaluate safety profile and efficacy outcomes of pts with cHL treated with 1L NAVD in a real-world setting (RWS). Methods: In this multicenter retrospective cohort study, we included pts ≥18 years with cHL treated with 1L standard of care NAVD between 2023 and 2025 at 20 US academic sites. The safety evaluable cohort received at least 1 cycle of NAVD and included pts who have not completed tx. The efficacy evaluable cohort had completed 6 cycles of tx including end of treatment (EOT) PET-CT and included pts who intended to complete tx but died or discontinued due to progressive disease or AEs. The primary endpoint was EOT overall response rate (ORR). Secondary endpoints included EOT complete response rate (CRR), PFS and overall survival (OS). PFS and OS were calculated from the start date of tx and analyzed using the Kaplan Meier method. Results: A total of 311 pts with cHL were treated with NAVD with 26% of pts with tx ongoing (n=83) and 73% with tx completed (n=228). Baseline demographics included 55% male pts, 60% with stage IV disease (stage IIB, n=4) and 84% with nodular sclerosis subtype. Median age was 37 years (range 18-88), 29% had bulky disease (>7.5 cm), 28% were EBV positive (n=74/268), 8% had history of an autoimmune disease, and 31% had an IPS 4-7. G-CSF was given in 64% of pts. All patients were safety evaluable. Tx was interrupted (any length) in 24%, reduced in 12%, and discontinued in 14%. The most common reason for dose reduction was neuropathy in 4%. Nivolumab was discontinued in 10% and all therapy in 3.7% due to toxicity. Any AE and any grade 3 or higher AE (>G3) were observed in 92% and 62%, respectively. Neutropenia of any grade occurred in 68% (48% >G3), infection in 25% (10% >G3), and neuropathy in 30% (2.8% >G3). Hospitalization for an AE occurred in 20% (4.5% febrile neutropenia). Among pts with complete data (n=305), any immune related AE (irAE) occurred in 78 pts (25.6%) with any >G3 irAE in 23 pts (7.5%). The most common irAEs included hypothyroidism (7.9%, all grade 1-2), hepatotoxicity (1.6% G1/G2, 3.3% >G3), inflammatory arthritis (3% G1/G2, 0.6% >G3), rash (2.6%, all grade 1-2), and colitis (1% G1/G2, 1% >G3). Other notable >G3 irAEs included adrenal insufficiency (n=2), AKI/ATN (n=1), myocarditis (n=1), diabetes (n=1) and pancreatitis (n=1). Of 84 irAE events, 47 (56%) have had complete resolution. Among all pts, 14.4% (n=45) required systemic steroids at any time (intravenous in 4.1%), 3.2% (n=10) require ongoing steroids/immunosuppression and 8.3% other therapy for an irAE (n=23 levothyroxine, n=1 hemodialysis, n=1 heart failure tx, n=1 insulin). Among all pts, 265 (85%) had an interim PET-CT after 2-4 cycles. The ORR and CRR at interim PET-CT were 97% and 78%, respectively. In the efficacy evaluable population (n=228), the EOT ORR and CRR were 96% and 90%. The median follow up was 10.2 mo (range 0.27-28.52). The 1-year PFS and OS estimates were 93.8% (95% CI: 90.8-98.4%) and 99.1% (95% CI: 97.9-100%), respectively. In multivariable analysis (MVA), only IPS score (OR 0.6, 95%CI: 0.59-0.60) was associated with lower CRR. In Cox univariable analysis, EBV+ status (HR=14.8, 95% CI: 3.2-69.2), IPS score (HR=1.5, 95% CI: 1.0-2.2), and ESR (HR=1.02, 95% CI: 1.00-1.04) were associated with worse PFS. Among the 11 pts with progression/relapse, 9 were primary refractory. 10 pts were started on second line (2L) therapy, and all pts are alive (1 pt pending 2L tx initiation). There were 2 deaths: one related to infectious complications and other unknown and both occurred after the first cycle of therapy. Conclusions: Pts treated with NAVD in a large RWS showed comparable response rates and 1-year survival outcomes to those in the pivotal S1826 trial. Most AEs were similar and grade 1-2, but close monitoring of irAEs is necessary given the potential long-term toxicity of checkpoint inhibitors and potential for ≥G3 irAEs (7.5%) in this young patient population. Our data supports the use of NAVD for 1L advanced stage cHL.
Multicenter real-world outcomes in limited stage (LS) diffuse large B-cell lymphoma (DLBCL) treated with abbreviated immunochemotherapy
Cherng, Hua-Jay, Gerber, Drew, Nze, Chijioke, Bhayani, Shahzeem, Russler-Germain, David, Alnughmush, Ahmed, Hampel, Paul, Kille, Kelsey, Wallace, Danielle, Qualls, David, Merryman, Reid, Brooks, Jaden, Bock, Allison, Ramirez, Juan, Zhang, Yumeng, Chavez, Julio, Granger, Katelynn, Antel, Katherine, Duarte, Cassandra, Major, Ajay, Ma, Sirui, Spinner, Michael, Mackay, Alyssa, Hu, Bei, Rai, Manoj, Spurgeon, Stephen, Lee, Benjamin, Doh, Jean, Brem, Elizabeth, Altomare, Nicole, Karmali, Reem, Ryan, Robert, Tiger, Yun Kyoung, Carter, Jordan, Landsburg, Daniel, Thiruvengadam, Swetha, Skarbnik, Alan, Choi, Yun, Bond, David, Samaeekia, Ravand, Ma, Helen, Tolu, Seda, Amengual, Jennifer, Herrera, Alex, Pro, Barbara, Qualls, David , Qualls, David A , Cherng, Hua-Jay, Gerber, Drew, Nze, Chijioke, Bhayani, Shahzeem, Russler-Germain, David, Alnughmush, Ahmed, Hampel, Paul, Kille, Kelsey, Wallace, Danielle, Merryman, Reid, Brooks, Jaden, Bock, Allison, Ramirez, Juan, Zhang, Yumeng, Chavez, Julio, Granger, Katelynn, Antel, Katherine, Duarte, Cassandra, Major, Ajay, Ma, Sirui, Spinner, Michael, Mackay, Alyssa, Hu, Bei, Rai, Manoj, Spurgeon, Stephen, Lee, Benjamin, Doh, Jean, Brem, Elizabeth, Altomare, Nicole, Karmali, Reem, Ryan, Robert, Tiger, Yun Kyoung, Carter, Jordan, Landsburg, Daniel, Thiruvengadam, Swetha, Skarbnik, Alan, Choi, Yun, Bond, David, Samaeekia, Ravand, Ma, Helen, Tolu, Seda, Amengual, Jennifer, Herrera, Alex, Pro, Barbara

Mayo Clinic

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 471-471

10.1182/blood-2025-471 Get It

Abstract Background: For LS-DLBCL, clinical trials (FLYER, LYSA/GOELAMS 02-03, LYSA LNH09-1B, S1001) have shown that 4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP4) without radiation (RT) leads to durable remissions in >90% of cases. However, only patients (pts) with non-bulky disease and/or international prognostic index (IPI) of 0 and complete metabolic response (CMR) on interim positron emission tomography (PET) scan, if performed, were eligible for RCHOP4 alone in these studies. Outcomes in trial-ineligible LS-DLBCL and the appropriate real-world candidates for RCHOP4 are still undefined. Methods: We conducted a multicenter retrospective study of adult pts with stage I/II DLBCL of any tumor bulk, IPI and with or without B-symptoms diagnosed after 2011 and treated with RCHOP4 +/- 2 cycles R from 21 U.S. centers. Pts with PMBCL, PTLD or receiving non-standard dose RCHOP for cycle (C) 1 or planned consolidative RT were excluded. The primary endpoint was PFS from C1 by Kaplan-Meier method, not counting indolent lymphoma relapse. Event free survival (EFS) was time to next therapy without progression (including unplanned RT for non-CR), progression or death. A competing risks analysis of non-relapse mortality (NRM) vs. DLBCL progression was performed. Results: The characteristics of the 428 pts were: median age 60 (18-88), 60% male, 11% Hispanic and 4% non-Hispanic Black, 62% stage I, 15% elevated LDH, 3% ECOG PS>1, 5% tumor bulk >7cm, 9% had B-symptoms and median Charlson Comorbidity Index (CCI) was 4 (2-12). IPI was 0, 1 and 2-3 in 42%, 46% and 12% and stage-modified IPI (smIPI) was 0, 1, 2 and 3-4 in 25%, 48%, 21% and 6% of pts. 66% had nodal (59% head/neck, 11% pelvic, 9% multiple above diaphragm, 7% abdominal) and 46% extranodal sites (37% head/neck, 20% gastric/intestinal, 9% spleen, 8% skin/soft tissue); 6% had transformed/concurrent FL/MZL or grade 3B FL, 33% (138/408) were non-GCB cell of origin (COO), 25% (90/357) double expressor (DEL) and 0.5% (2/379) double-hit. 13% had completely resected disease, 97% staging PET and 47% bone marrow biopsy. Median diagnosis to treatment interval was 30 days (IQR 20-43), 6% had dose reductions after C1, 77% had an interim PET (iPET) after C2 (33%) or C3 (67%), 15% received 2 additional cycles R and 4% CNS prophylaxis. CMR rates by iPET were 83% after C2 and 94% after C3, and 95% by end-of-treatment PET. iPET PMR was more likely if smIPI>2 or bulky disease. Median follow-up time was 2.7 years. There were 32 progression events: 14 occurred at the primary site and 17 at distant sites (1 unknown), and 12 occurred after 2 years. Another 11 pts received unplanned RT after RCHOP4 for non-CR. There were 24 deaths, 12 without prior progression. Cause of death was DLBCL in 7 and non-DLBCL in 17 cases (6 infection, 2 ILD, 2 heart failure, 2 second cancer, 1 seizure, 4 unknown). EFS, PFS and OS rates were 88%, 90% and 96% at 3 years. By univariable Cox regression, Black race, elevated LDH, smIPI>2, DEL, increasing CCI, multiple subdiaphragmatic nodal sites and iPET PMR were associated with worse PFS. Non-significant variables of note included COO, extranodal sites, complete resection, missing bone marrow biopsy, missing iPET and additional cycles R. By multivariable analysis (including age>60, stage, ECOG PS>1, elevated LDH, bulky disease, CCI, B-symptoms and DEL), ECOG PS>1 (HR 3.95 p=0.050), CCI (HR 1.29 p=0.003) and DEL (HR 2.02 p=0.069) were associated with worse PFS. Cumulative incidence of DLBCL progression and NRM were 8% and 2% at 3 years. Competing risk analysis by univariable models found that age>60, ECOG PS>1, smIPI>2, elevated LDH, CCI and bulky disease were associated with NRM, while DEL and B-symptoms were associated with DLBCL progression.Conclusion: Presented is the largest retrospective cohort of LS-DLBCL treated uniformly with RCHOP4 to date. Despite modest follow-up time and lack of an “intention-to-treat“ population, this study shows that abbreviated RCHOP4 leads to excellent outcomes in the real-world, albeit with continuous risk of late relapse. smIPI risk factors were associated with worse PFS, though this may in part be driven by risk of non-lymphoma death. As pts with advanced age, poor performance status or comorbidities may benefit from reduced treatment exposure, RCHOP4 should still be considered for these and other “trial-ineligible” pts, particularly if other high-risk features (iPET PMR, DEL or B-symptoms) are absent.
Twelve month landmark analysis of outcomes of relapsed or refractory large B-cell lymphoma patients achieving prolonged remission with glofitamab or epcoritamab in the real-world outcomes of bispecific T-cell engagers (REALBiTE) multi-center, retrospective
Brooks, Taylor, Nedved, Adrienne, Wang, Yucai, Grover, Natalie, Yang, XI, Karimi, Yasmin, Schwarz, Tenley, Schwede, Matthew, McKenna, Marshall, Tiger, Yun Kyoung, Abdel-Razeq, Nayef, Moustafa, Muhamad Alhaj, Reinert, Catherine, Major, Ajay, Trotier, Daniel, Pophali, Priyanka, Baron, Kelsey, Hu, Boyu, Jones, Sally, Saha, Aditi, Dave, Nikita, Landsburg, Daniel, Sears-Smith, Megan, Ghosh, Nilanjan, Salafian, Kiarash, Ayers, Emily, Sundaram, Suchitra, Brody, Joshua, Gibson, Alyssa, Kline, Justin, Munoz, Javier, Morales, Rodolfo Garza, Khan, Eiraj, Khan, Cyrus, Castillo, Brenda, Smith, Stephen, Chinyengetere, Fadzai, Dave, Sandeep, Niu, Alex, Hernandez-Ilizaliturri, Francisco, Caimi, Paolo, Hill, Brian, Karimi, Yasmin , Karimi, Yasmin H , Brooks, Taylor, Nedved, Adrienne, Wang, Yucai, Grover, Natalie, Yang, XI, Schwarz, Tenley, Schwede, Matthew, McKenna, Marshall, Tiger, Yun Kyoung, Abdel-Razeq, Nayef, Moustafa, Muhamad Alhaj, Reinert, Catherine, Major, Ajay, Trotier, Daniel, Pophali, Priyanka, Baron, Kelsey, Hu, Boyu, Jones, Sally, Saha, Aditi, Dave, Nikita, Landsburg, Daniel, Sears-Smith, Megan, Ghosh, Nilanjan, Salafian, Kiarash, Ayers, Emily, Sundaram, Suchitra, Brody, Joshua, Gibson, Alyssa, Kline, Justin, Munoz, Javier, Morales, Rodolfo Garza, Khan, Eiraj, Khan, Cyrus, Castillo, Brenda, Smith, Stephen, Chinyengetere, Fadzai, Dave, Sandeep, Niu, Alex, Hernandez-Ilizaliturri, Francisco, Caimi, Paolo, Hill, Brian

Mayo Clinic

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 4499-4499

10.1182/blood-2025-4499 Get It

Abstract Introduction: Epcoritamab (epco) and glofitamab (glofit) are bispecific antibodies (BsAbs) approved for the treatment of patients (pts) with relapsed or refractory (r/r) large B-cell lymphomas (LBCLs). Their use is associated with relatively high response rates, with some patients experiencing prolonged remission. It is unclear whether continuous treatment beyond 12 months for pts in remission is beneficial, as continued immunosuppression may result in additional toxicity. We sought to report the outcomes of pts with prolonged remission and survival following BsAb administration. Methods: We performed a multicenter retrospective study including 21 US centers evaluating pts with r/r LBCLs receiving commercially available epco or glofit between 2023 and 2025. Baseline characteristics and outcomes were extracted from medical records. Efficacy and survival outcomes were assessed by site investigators and included overall response rate (ORR), complete and partial response (CR, PR) rates. Pts who responded to BsAbs and had ≥365 days of follow-up from initiation of BsAb treatment were included in the analysis. Results: As of May 15, 2025, a total of 312 pts with r/r LBCLs were treated with BsAbs (epco n=193, glofit n=119) with a median age of 66 years (interquartile range [IQR] 59-73) at BsAb start. Most were male (64.5%), had advanced stage disease (77.4%) and had ECOG performance status of ≤1 (93.3%) at BsAb start. Of 207 pts who had initiated treatment with BsAb ≥12 months prior to data cutoff, we identified 31 pts (15.0%) who had a response to BsAbs (19 epco, 12 glofit) and were alive without progression at 12-months post-BsAb initiation and included them in this landmark analysis. Of the cohort of 19 pts treated with epco, 6 discontinued due to reasons other than disease progression including CAR-T cell therapy (n=2), secondary malignancy (n=2), allogeneic transplant (n=1), or other reasons (n=1). Thirteen of 19 pts received ≥12 months of epco treatment, and, with a median follow-up of 16 months from the start of BsAb, 12 of 13 pts continued receiving epco beyond 12 months with one pt discontinuing after 12 months (observed for an additional 41 days prior to censoring). Of the cohort of 12 pts treated with glofit, 8 pts were observed after completing all planned therapy and 4 patients underwent allogeneic transplant. Among all 31 BsAb-treated patients alive and in remission at 12 months, at the time of data cutoff, 5 pts (12.9%) had progressed (2 previously treated with epco and 3 with glofit). Three of the 4 pts who underwent allogeneic transplant after prior glofit treatment experienced disease relapse. A total of 24 pts (77.4%) were alive at the time of last follow-up, with the causes of death being disease progression (n=1), secondary malignancy (n=1), infection (n=1), and unknown cause (n=4). Conclusions: In this large cohort of r/r LBCL pts treated with BsAbs monotherapy in the standard of care setting, a relatively small proportion of pts (15%) achieve the 12 month PFS landmark. In the absence of robust evidence for what constitutes best practice, different strategies are employed, including continuation of BsAb, observation as well as consolidation with allogeneic transplant or CAR T-cell therapy. Additional follow-up will be reported to help guide clinical decision making regarding the optimal management strategy for this high risk pt population.
Comparison of real-world survival outcomes and time toxicity of CAR T-cell versus bispecific antibody therapies in relapsed/refractory follicular lymphoma: A multicenter cohort from 15 US academic institutions
Abbott, Diana, Amorim, Ana , Houshyar, Samin , Adhikari, Arjab, Patel, Dilan A. , Wanjiku, Christopher, Bock, Allison M. , Any, Haya Al, Desai, Nidhi , Gupta, S. C. , Altomare, Nicole , Trotier, Daniel, Ricker, Edd , Hill, Brian T. , Gupta, Supriya , Major, Ajay , Abbott, Diana , Snyder, Jordan Andrew , Ahmed, Nausheen , Villasboas, José C. , Sharp, John, Voorhees, Timothy , Wallace, Danielle, Wagner, Charlotte B , Brooks, Taylor , Tsang, Mazie , Rajab, Mohamed , Iqbal, Madiha , Gupta, Supriya, Karmali, Reem , Pophali, Priyanka A. , Cherng, Hua‐Jay J. , Gupta, Arjun

Mayo Clinic

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 1798-1798

10.1182/blood-2025-1798 Get It

Abstract Background Chimeric antigen receptor T-cell (CAR-T) and bispecific antibody (BsAb) therapies are both effective for patients with relapsed/refractory (R/R) follicular lymphoma (FL), but differ in treatment schedules and associated “time toxicity,” or contact days spent physically interacting with the healthcare system. While contact days can be estimated from clinical trials, real-world data provides a more nuanced depiction of treatment-related time burden, which may guide treatment decision-making. The comparative time toxicity of CAR-T vs BsAb in R/R FL is not defined. Methods We conducted a multicenter retrospective study of adults with R/R grade 1-3A FL who received standard-of-care CAR-T (axi-cel, tisa-cel, liso-cel) or BsAb (mosunetuzumab, epcoritamab) in the third-line or later setting before Jan 1, 2025. Time toxicity was defined as outpatient or inpatient days with physical health care system contact, counting multiple visits on the same day as only one day. All days after treatment initiation were counted, regardless of disease progression, therapy completion, or relation to FL therapy. Median contact days over 1-year time horizon were compared, stratified by CAR-T vs BsAb, prior lines of therapy (LOT, 2 vs 3+), and time intervals (0-1, 1-3, 3-6, 6-9, and 9-12 months). Progression-free survival (PFS) and overall survival (OS) were calculated from day of CAR-T infusion or day 1, cycle 1 for BsAb. Cox regression and propensity matching (by age, ECOG, refractory to prior LOT, POD24) were used to assess predictors and survival associations with contact days. Results Among 209 patients from 15 U.S. academic centers, median age was 64, 37% were female, 61% received CAR-T (80% axi-cel, 7% liso-cel, 13% tisa-cel) and 39% BsAb (93% mosun, 7% epcor). Most had Grade 1-2 FL (72%), advanced stage (84%), and extranodal disease (51%). Median prior LOT was 3 (range 2-15), 41% were refractory to prior LOT, and 52% had POD24. Median number of BsAb doses was 10 (range 1-36). Patients receiving BsAb were significantly older (p<.01) and had higher CIRS comorbidity scores (p<.02) in both 2 and 3+ prior LOT cohorts, and had higher ECOG scores (p=.01) and were less likely to be refractory to prior LOT (p=.029) in 3+ LOT cohort. There were no differences in POD24 rates between CAR-T and BsAb. Median PFS for the entire cohort was 3.6 yrs; median OS was not reached. In the 2 prior LOT cohort (N=75), 60% received CAR-T and 40% BsAb. With median follow-up of 1.5 years, median PFS was not reached for CAR-T and 1.6 yrs for BsAb (p<.0001). In the 3+ prior LOT cohort (N=134), 62% received CAR-T and 38% BsAb. With median follow-up of 2 yrs, median PFS was 3.6 yrs for CAR-T and 1.6 yrs for BsAb (p=.0044). In propensity matched analysis, PFS was shorter for BsAb in both 2 LOT (HR 9.0, 95% CI 1.14-71.04, p=.037) and 3+ LOT (HR 3.25, 95% CI 1.06-9.97, p=.039) cohorts as compared to CAR-T. There were no significant differences in OS between CAR-T and BsAb. Median contact days were significantly higher for CAR-T vs BsAb in the 0-1 month interval: 19 vs 8 days in 2 LOT (p<.0001) and 18 vs 7 days in 3+ LOT (p<.0001) cohorts. There were no differences in contact days between CAR-T vs BsAb in subsequent time intervals. Over 1 year, CAR-T had significantly more time toxicity than BsAb: median 51 vs 36 contact days in 2 LOT (p<.0001) and 64 vs 38 days in 3L+ LOT (p<.0001) cohorts; these remained significant in the matched analysis. B symptoms (p=.04) and Grade ≥3 cytopenias (p=.007) were associated with higher contact days in 3+ LOT cohort in univariable analysis. Higher contact days were associated with inferior PFS (HR 1.01, 95% CI 1.00-1.02, p=.032) and OS (HR 1.01, 95% CI 1.00-1.02, p=.038) in 3+ LOT cohort regardless of treatment type. Discussion In this large real-world cohort of patients with R/R FL, CAR-T therapy resulted in better PFS but more time toxicity over the first year as compared to BsAb therapy. Excess time toxicity from CAR-T was driven by more contact days in the first month of treatment. This study provides benchmark data for counseling patients about expected time burden of CAR-T (51-64 days) and BsAb (36-38 days) over the first year of these therapies. Further, with superior PFS of CAR-T in this study and minimal impact of time toxicity on survival outcomes, these data can be used to better support shared decision-making in R/R FL by addressing patient preferences regarding both contact days as well as duration of disease control.
Cell-of-Origin Subtype Predicts Response to Polatuzumab Vedotin in Large B-cell Lymphoma
Cliff, Edward R. Scheffer , Pelaez, Guido D. , Wan, Fei , Iyengar, Varun , Zhou, Jihao , Chung, Kevin , Abdel-Razeq, Nayef , Allen, J. , Major, Ajay , Sharp, John , Gould, Patrick , Houshyar, Samin , Lynch, Ryan C. , Fleyshman, Michelle , Kidwell, Adam , Fenske, Timothy S. , Malakhov, Nikita , Mulvey, Erin , Nowakowski, Grzegorz S. , Torka, Pallawi , Russler‐Germain, David A. , Allen, Jessica , Epperla, Narendranath , Gould, Patrick , Cherng, Hua-Jay J , Houshyar, Samin , Wallace, Danielle S , Lynch, Ryan C , Kallam, Avyakta , Mei, Matthew , Merryman, Reid W , Fleyshman, Michelle , Rhodes, Joanna , Kidwell, Adam , Fenske, Timothy S , Malakhov, Nikita , Mulvey, Erin , Watkins, Marcus , Moustafa, Muhamad Alhaj , Hilal, Talal , Nowakowski, Grzegorz S , Wang, Yucai , Torka, Pallawi , Russler-Germain, David A , Major, Ajay , Sharp, John , Zhou, Jihao , Epperla, Narendranath , Cherng, Hua‐Jay J. , Wallace, Danielle , Kallam, Avyakta , Mei, Matthew , Merryman, Reid W. , Rhodes, Joanna , Watkins, Marcus P. , Moustafa, Muhamad Alhaj , Hilal, Talal , Wang, Yucai

Mayo Clinic

Clinical Cancer Research | October 27, 2025 | Volume: 32 | Issue: 1 | Pages: 159-168

10.1158/1078-0432.ccr-25-2392 | PMID 41143601 Get It

Abstract Purpose: Polatuzumab vedotin (polatuzumab) was approved for up-front treatment of diffuse large B-cell lymphoma in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell of origin (COO), polatuzumab seems to have greater efficacy in activated B-cell than germinal center B-cell (GCB) subtype disease. Most studies of polatuzumab used RNA expression to assess COO, whereas in routine clinical practice, the immunohistochemistry-based Hans algorithm is used. Experimental Design: To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with large B-cell lymphoma (LBCL) receiving polatuzumab from 2015 to 2024, split by receipt of polatuzumab in first-line versus relapsed/refractory settings. The primary endpoint was overall response rate (ORR) to polatuzumab-based treatment in GCB versus non-GCB relapsed/refractory LBCL. Results: Of 740 patients, 305 received polatuzumab in the first-line setting and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, the ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% [OR, 2.6; 95% confidence interval (CI), 1.77–3.84; P < 0.0001], with a complete response rate of 35.7% versus 17.7% (OR, 2.6; 95% CI, 1.66–4.02; P < 0.0001). Progression-free survival was longer for patients with non-GCB versus GCB COO (HR, 0.64; 95% CI, 0.5–0.83; P = 0.0006). In the first-line cohort, ORR, complete response rate, and progression-free survival were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting that the addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP. Conclusions: Based on these data, COO classification by the Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.
Real-world outcomes of patients with aggressive B-cell lymphoma treated with epcoritamab or glofitamab
Brooks, Taylor , Zabor, Emily C. , Bedelu, Yohanna B., Yang, Xi , Karimi, Yasmin , Nedved, Adrienne, Wang, Yucai , Dave, Nikita, Baron, Margaret Kelsey , Trotier, Daniel, Miller, Jordan A. , Reinert, Catherine, Schwarz, Tenley, Salafian, Kiarash , Ayers, Emily C. , McKenna, Marshall, Tiger, Yun Kyoung , Sears-Smith, Megan , Peterson, Chelsea , Khan, Cyrus, Bliven, Sean Patrick , Narkhede, Mayur , Gibson, Alyssa, Munoz, Javier, Smith, Stephen D. , Hernandez‐Ilizaliturri, Francisco J. , Chinyengetere, Fadzai, Davé, Sandeep S. , Abdel-Razeq, Nayef , Hill, Brian T. , Brooks, Taylor R , Karimi, Yasmin H , Baron, Kelsey , Trotier, Daniel C , Pophali, Priyanka , Grover, Natalie S , Major, Ajay , Salafian, Kiarash , Ayers, Emily C , Brody, Joshua D , Sears-Smith, Megan , Peterson, Chelsea , Bliven, Sean P , Garza-Morales, Rodolfo , Ho, Carrie , Smith, Stephen D , Niu, Alex , Moustafa, Muhamad Alhaj , Wang, Yucai , Landsburg, Daniel J. , Hu, Boyu , Pophali, Priyanka A. , Grover, Natalie S. , Major, Ajay , Patel, Krish , Sundaram, Suchitra , Brody, Joshua , Ghosh, Nilanjan , Kline, Justin Paul , Munoz, Javier, Garza-Morales, Rodolfo , Niu, Alex , Moustafa, Muhamad Alhaj , Caimi, Paolo F.

Mayo Clinic

Blood | July 15, 2025 | Volume: 146 | Issue: 18 | Pages: 2177-2188

10.1182/blood.2025029117 | PMID 40663785 Get It

Abstract Epcoritamab and glofitamab are CD20-directed bispecific antibodies (BsAbs) approved in the United States for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Limited data exist for patients treated outside of trials. Patients with R/R DLBCL receiving commercial epcoritamab or glofitamab between 1 January 2023 and 15 October 2024 were collected from 21 United States institutions. Among 245 patients, 156 received epcoritamab and 89 received glofitamab, 113 were refractory to front-line therapy, 40 had MYC and BCL2 and/or BCL6 rearrangements, 147 received prior chimeric antigen receptor T-cell therapy, and 174 patients would have been ineligible for registrational trials. The overall response rate (ORR) for epcoritamab and glofitamab was 51% (23% complete response, [CR]) and 53% (30% CR), respectively. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 2.0-3.8 months), and median overall survival (OS) was 7.8 months (95% CI, 6.2-11.0 months). The 6-month PFS was 36% (95% CI, 30-44) and the 6-month OS was 60% (95% CI, 54-67). Both trial ineligibility and undetectable CD20 pre-BsAbs portended shorter PFS and OS. Of 17 individuals with paired biopsies, 15 (88.2%) lost CD20 expression after BsAbs with a median time to progression of 3.7 months. This analysis including patients with R/R DLBCL shows the ORR to CD3/CD20 BsAbs was comparable to pivotal trials, although PFS and OS were lower. Baseline undetectable levels of CD20 were associated with poor outcomes. These results demonstrate the activity of BsAbs in R/R DLBCL, and underscore the importance of target antigen expression.
23 | RADIOTHERAPY IMPROVES PROGRESSION‐FREE SURVIVAL FOR STAGE IA NLPHL: A RETROSPECTIVE REPORT FROM THE GLOBAL NLPHL ONE WORKING GROUP (GLOW)
Hartmann, S., Eich, Hans‐Theodor, Skinnider, Brian, Akhtar, Saad , Steiner, R., Milgrom, Sarah A. , Alomari, Mohammed H., Zhang, X., Wirth, A., Tsang, Rky, Smith, Sonali M. , Hendrickson, P., Hopkins, David , Ng, A., Koenig, Julie L. , Casulo, Carla , Sakthivel, GD, Roberts, Kenneth B. , Gao, Sarah , Alkendi, Jalila , Rahbi, Nasser Al, Balogh, Alex, Ricardi, U., Torka, Pallawi , Silva, Ravi De , Shah, Nimish , Osborne, Wendy , Henry, M M , Miall, Fiona , Brady, J.L. , Mikhaeel, G., Brennan, Barbara J. , Penn, Andrew M. , Reeves, Michael A., Terezakis, S., Kirova, Youlia , Fergusson, Pamela, Lee, Denise , Ku, Matthew , Mutsando, Howard , Tedjaseputra, Aditya , Gilbertson, Michael , Marconi, Tamara , Viiala, Nicholas , Natkunam, Y., Kelly, Kara M. , Borchmann, Peter , Hoppe, R T, Binkley, Michael S., Hopkins, David , Ku, Matthew , Flerlage, Jamie E. , Eichenauer, Dennis A. , Fuchs, M., Hartmann, S., Savage, Kerry J. , Hodgson, David C. , Rauf, M. Shahzad , Maghfoor, Irfan , Pinnix, Chelsea C. , Vega, Francisco , Alomari, M., Zhang, X., Collins, Graham P. , Advani, Ranjana H. , Kumar, P., Dickinson, Michael , Tsang, R., Prica, Anca A. , Major, Ajay , Kelsey, Chris R. , McKay, Pamela , Constine, Louis S , Casulo, Carla , Baron, J., Plastaras, John Peter , Levis, Mario , Sridhar, A., Specht, Lena , Pickard, Keir , Blazin, Lindsay , Henry, M., Chang, I., Smith, Christine M , Halperin, Daniel M. , Brennan, B., Penn, A., Senchenko, Maria Anatolevna , Volchkov, Egor Vasilevich , Hoppe, Bradford S. , Talaulikar, Dipti , Pepa, Roberta Della , Picardi, Marco , Fergusson, P., Northend, Michael , Hawkes, Eliza A. , Doo, Nicole Wong , Barraclough, Allison , Opat, Stephen , Cheah, Chan Y. , Salvaris, Ross , Hamad, Nada , Palese, M., Shankar, Ananth , Maurer, Matthew J. , Binkley, Michael S.

Mayo Clinic

Hematological Oncology | June 16, 2025 | Volume: 43 | Issue: S3 | Pages: No page available

10.1002/hon.70093_23 Get It

419 | MULTICENTER REAL‐WORLD OUTCOMES IN DIFFUSE LARGE B‐CELL LYMPHOMA PROFILED WITH A COMMERCIALLY‐AVAILABLE CIRCULATING TUMOR DNA ASSAY
Gould, P., Ma, Xin , Ananth, Sudha , Rose, Alan, Lattin, John , Skarbnik, Alan P , Bock, Allison M. , Baron, Kelly Glazer , Hess, Brian , Ayers, Edward L., Pro, Barbara, Vaidya, S., Amengual, Jennifer E. , Godbole, S., Bond, David A. , Ananth, S., Jacobs, Ryan W. , Hu, Bei , Stanchina, Michele , Rose, A., Russler‐Germain, David A. , Randall, Michael P. , Spinner, Michael A. , Duarte, C., Major, Ajay , Baron, K., Ip, Andrew , Tsang, Mazie , Ayers, E., Tolu, Seda , Reshef, Ran , Cherng, Hua‐Jay J.

Mayo Clinic

Hematological Oncology | June 16, 2025 | Volume: 43 | Issue: S3 | Pages: No page available

10.1002/hon.70094_419 Get It

572 | PATIENT‐REPORTED OUTCOMES IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA PATIENTS TREATED WITH EPCORITAMAB: OVERALL AND SUBGROUP ANALYSIS BY BASELINE SYMPTOM BURDEN
Johnson, P. C., Nsiah, Irene , Ding, Zhijie , Mutebi, Alex , Patah, Poliana, Favaro, Enrico, Dueck, Amylou C. , Ghione, Paola , Major, Ajay , Wang, Anthony , Alshreef, Abualbishr , Yu, Jovian , Favaro, E., Jurczak, Wojciech

Mayo Clinic

Hematological Oncology | June 15, 2025 | Volume: 43 | Issue: S3 | Pages: No page available

10.1002/hon.70096_572 Get It

Vulnerable Elders Survey (VES-13) and Longitudinal Analysis of Quality of Life in Indolent Non-Hodgkin Lymphoma: A Multi-Institutional Prospective Cohort Study
Thompson, Carrie A. , Hildebrandt, Michelle A.T., Yost, Kathleen J. , Gysbers, Brianna, Tilburt, Jon C. , Koehler, Amber B. , Call, Timothy G. , Thanarajasingam, Gita , Nowakowski, Grzegorz S. , Cohen, Jonathon B. , Strouse, Christopher , Lossos, Izidore S. , Martin, Peter W., Flowers, Christopher R. , Strouse, Christopher S , Tsang, Mazie , Noble, Brie N. , Casulo, Carla , Rosenthal, Allison , Chihara, Dai , Mou, Eric , Durani, Urshila , Williams, Annalynn M , Hildebrandt, Michelle A.T. , Larson, Melissa C. , Maurer, Matthew J. , Feldman, Andrew L. , Jaye, David L. , Major, Ajay , Hilal, Talal , Wang, Yucai , Parikh, Sameer A. , Muñoz, Javier , Nastoupil, Loretta J. , Cohen, Jonathon B. , Habermann, Thomas M. , Kahl, Brad S. , Martin, Peter, Cerhan, James R. , Dueck, Amylou C.

Mayo Clinic

Blood | December 6, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 2345-2345

10.1182/blood-2024-210594 Get It

Background: Indolent non-Hodgkin lymphomas (iNHL) are incurable and disproportionately affect adults age >65 in whom frailty and functional impairment can impact disease management. The Vulnerable Elders Survey (VES-13) is a 13-item screening tool that incorporates age, self-rated health, physical function limitations, and functional disabilities to identify vulnerable older community-dwelling adults. Adults with a VES-13 score of >3 have a fourfold increased risk of death or functional decline over 2 years as compared to adults with a score <3 (Saliba et al, JAGS 2001). Our team previously showed that VES-13 >3 was associated with a higher risk of 1-year mortality in NHL (OR 3.26, 95% CI 2.15-4.96, Fama et al, ASH 2019), including in adults age <65. In this study, we determined whether VES-13 scores >3 were associated with quality of life (QOL) changes in adults with iNHL across the age spectrum. Methods: We used the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study to identify adults enrolled from 2015-2020 with grade 1-3A follicular and marginal zone lymphoma (FL, MZL) who completed the VES-13 at enrollment and QOL surveys at enrollment and follow-up. The LEO Cohort Study enrolls participants within 6 months of diagnosis and collects information on disease status, QOL, health behaviors, and patient-reported functional assessment. For this analysis we included QOL measured using the Functional Assessment of Cancer Therapy-General (FACT-G) at years 1 and 2 post-enrollment. The FACT-G total score was the sum of 4 subscales (range): physical (PWB, 0-28), social/family (SFWB, 0-28), emotional (EWB, 0-24), and functional (FWB, 0-28) well-being. A higher FACT-G total score (range 0-108) indicated better overall QOL. VES-13 scores ranged from 0 (lowest risk for death or decline) to 10+ (highest risk). Generalized linear mixed models evaluated changes in QOL from baseline based on VES-13 score >3 (vulnerable) vs <3 (non-vulnerable), within groups by age at enrollment >65 and <65. Results: Our study included 1,186 participants: 42% age >65, 54% female, 84% non-Hispanic White, 10% Hispanic, 3.3% Black, and 1.4% Asian/Pacific Islander. Most (68%) were diagnosed with FL. FLIPI was high risk for 20%, and MALT-IPI was high risk for 23%. In the VES-13 <3 group, the mean (SD) baseline FACT-G total score was 86.5 (12.0), PWB 21.0 (3.5), SFWB 24.3 (4.3), EWB 18.8 (3.7), and FWB 22.3 (4.9). In the VES-13 >3 group, the mean (SD) baseline FACT-G total score was 70.4 (16.5), PWB 15.4 (5.6), SFWB 22.3 (5.5), EWB 17.5 (4.5), and FWB 15.3 (6.4); all significantly lower than the VES-13 >3 group (all p<0.01). In adults <65, 63 (9%) had a VES-13 >3, which was associated with a significant improvement from baseline in PWB at years 1 and 2 when compared to VES-13 <3 (changes in baseline PWB were 2.1, 2.9 for VES-13 >3 vs 0.2, 0.1 for VES-13 <3, all p<0.05). Similarly, we observed improvement in FWB from baseline at years 1 and 2 in the VES-13 >3 vs <3 group (2.4, 2.9 vs 0.4, -0.1, respectively all p<0.05). The VES-13 >3 group had a decline in their EWB at 1 year vs the VES <3 group (-0.5 vs 1.2, respectively, p=0.003). At year 2, total FACT-G improved from baseline in the VES-13 >3 group (5.6 for VES-13 >3 vs -0.5 for VES-13 <3, p=0.002). SFWB changes from baseline did not differ between groups. In adults >65, 83 (17%) had a VES-13 >3, which was associated with a significant improvement from baseline PWB (1.3, 1.5 for VES-13 >3 vs. 0.1, -0.1 for VES-13 <3), FWB (3.3, 2.2 for VES-13 >3 vs. 0.5, 0.1 for VES-13 <3), and total FACT-G score (5.2, 3.4 for VES-13 >3 vs. 1.0, -0.4 for VES-13 <3) when compared to VES-13 <3 at years 1 and 2 (all p<0.05). SFWB and EWB changes from baseline did not differ between groups. While there was improvement from baseline PWB and FWB in the VES-13 >3 group, QOL scores across all subscales remained below the VES-13 <3 group in the study period for both age groups. Statistical significance was maintained in models adjusted for baseline characteristics, including initial treatment strategy (observation, systemic, vs local) for both age groups. Conclusion: Although the vulnerable group reported worse QOL throughout the study period compared to the non-vulnerable group, survivors in the vulnerable group saw greater improvement in their physical and functional well-being at 1- and 2-years post-diagnosis. Additional analyses are underway to identify drivers of improvement in physical and functional well-being in vulnerable adults diagnosed with iNHL.