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Real-world outcomes and subsequent treatment utilization following anti-B-cell maturation antigen antibody-drug conjugate exposure in patients with multiple myeloma.
Dimopoulos, M A, Urrea, Jorge Monge, Kastritis, E K, Leleu, Xavier P., Siegel, David Samuel DiCapua, Ocio, Enrique M., Nagaraj, Madhu , Hassan, Rafla , Jagannath, Sundar, Weisel, K, Bonar, Nicolle , Green, Jeannette, Kroog, Glenn S. , Ma, Qiufei, Kumar, Shaji, Leleu, Xavier , Ocio, Enrique M. , Jagannath, Sundar , Weisel, Katja C , Shokoohi, Mostafa , Hampp, Christian , Humblet, Olivier , Breskin, Alexander , Ma, Qiufei , Kumar, Shaji

Mayo Clinic

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2026.44.16_suppl.e19503 Get It

e19503 Background: The anti-B-cell maturation antigen (BCMA) antibody-drug conjugate (ADC) belantamab mafodotin is approved in the USA and EU for relapsed/refractory multiple myeloma (RRMM). Understanding treatment options and patient outcomes following ADC failure is clinically important. This study describes post-ADC treatment patterns and clinical outcomes in real-world patients with RRMM. Methods: Adult patients with MM who received an ADC and initiated ≥1 subsequent line of therapy (LOT) were included. The index date was the start of the first post-ADC LOT. Data were obtained from chart reviews at International Myeloma Foundation International Myeloma Working Group (IMF IMWG) academic sites, and US electronic health records from largely community sites (COTA and Guardian Research Network [GRN]). Patient characteristics and index regimens were summarized descriptively. Time to next treatment (TTNT) and overall survival (OS) were estimated with the Kaplan-Meier estimator. Results: The IMF IMWG cohort (n=40) had a mean age of 70.8 years, median of 7 prior LOTs and 82.5% were triple-class refractory (TCR). Overall, 85% received ADC monotherapy (70% belantamab mafodotin) and 15% combination therapy. Pre-ADC and not considering corticosteroids, patients were commonly exposed to lenalidomide (R; 100%), bortezomib (V; 92.5%), daratumumab (D) and pomalidomide (P; 90% each). Over a median follow-up of 26 months after index date, 29 unique index post-ADC regimens were reported, frequently selinexor (27.5%) and bispecific antibodies (15%). CAR T-cell therapy was administered to 5%, with 60% re-treated with a pre-ADC drug class (PI/IMiD/anti-CD38) after ADC. Median (95% CI) TTNT and OS were 10.8 (7.0–20.6) and 19.0 (13.4–25.1) months, respectively. The COTA-GRN cohort (n=39) had a mean age of 67.5 years, median of 8 prior LOTs, and 51.3% were TCR. Overall, 56% received ADC monotherapy (belantamab mafodotin) and 44% combination therapy. Pre-ADC and not considering corticosteroids, patients were commonly exposed to D and R (97.4% each), and carfilzomib, V and P (94.9% each). Over a median follow-up of 9.2 months, 32 unique index post-ADC regimens were reported, frequently selinexor (23.1%) and venetoclax (17.9%) based; 0% received CAR Ts and 54% were re-treated with a pre-ADC drug class (PI/IMiD/anti-CD38) after ADC. Median (95% CI) TTNT and OS were 4.9 (2.8–non-estimable [NE]) and 12.0 (4.9–NE) months, respectively. Conclusions: Findings highlight that most patients with heavily pretreated BCMA-ADC exposed MM were re-treated with similar classes. Academic centers used novel therapies (ie, CAR T, bispecific antibodies) more often and their patients had longer survival than those treated at community sites. However, clinical outcomes remained sub-optimal, emphasizing the unmet need for effective, accessible post-ADC treatments.
Age and frailty analyses of transplant-ineligible (TIE) patients (pts) with newly diagnosed multiple myeloma (NDMM) in the phase 3 MAIA and CEPHEUS trials of daratumumab + lenalidomide-dexamethasone (Rd) and bortezomib-Rd (VRd).
Venner, Christopher P., Zweegman, Sonja, Kumar, Shaji, Facon, Thierry, Perrot, Aurore, Moreau, Philippe, NS, Raje, Hulin, Cyrille, Hungria, Vania, Cohen, Yaël , Goldschmidt, H, Wang, George C., Bolyard, Kasey, Lopez-Masi, Lorena, Loi, Matteo, Borgsten, Fredrik, Rowe, Melissa, Bahlis, Nizar Jacques J., Usmani, Saad Z., Zweegman, Sonja , Kumar, Shaji , Facon, Thierry T.F. , Perrot, Aurore , Moreau, Philippe , Hulin, Cyrille , Basu, Supratik , Goldschmidt, Hartmut , Bahlis, Nizar Jacques , Usmani, Saad Z.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 7569-7569

10.1200/jco.2026.44.16_suppl.7569 Get It

7569 Background: MAIA and CEPHEUS trials demonstrated that daratumumab (Dara) with standard of care (SOC) VRd or Rd significantly improved clinical outcomes versus SOC in TIE NDMM. Here we describe efficacy and safety in TIE pts from both trials by age and baseline (BL) frailty using the latest data cuts. Methods: Pts were randomized 1:1 to DRd (n=368) or Rd (n=369) in MAIA and 1:1 to DVRd (n=144) or VRd (n=145) in CEPHEUS. Progression-free survival (PFS), complete response or better (≥CR), overall MRD negativity (neg) at 10 -5 with ≥CR, sustained MRD neg with ≥CR (confirmed MRD neg ≥12 ± 1 months [mo] apart without MRD positivity in between), and safety were assessed by age (<70, 70–<75, or ≥75 years [y]) and BL frailty (assessed by IFM simplified frailty score: 0–1, non-frail; ≥2, frail). Results: Median follow-up was 64.5 mo in MAIA and 76.0 mo in CEPHEUS. In MAIA, 155 (21%) pts were <70 y, 261 (35%) 70–<75 y, and 321 (44%) ≥75 y; 341 (46%) pts were frail, 88.0 % of whom were ≥70 y. In CEPHEUS TIE pts, 70 (24%) pts were <70 y, 133 (46%) 70–<75 y, and 86 (30%) ≥75 y; 83 (29%) pts were frail, 86% of whom were ≥70 y. DRd or DVRd improved PFS, MRD neg rates, sustained MRD neg rates, and ≥CR rates vs Rd or VRd arms across age and frailty subgroups in both trials (Table). Safety was consistent with established individual drug profiles, and adverse event rates were generally comparable across treatment arms and subgroups within both trials. Additional data on patient-specific factors relevant to these subgroups will be presented. Conclusions: Dara-based regimens improved efficacy outcomes across subgroups in MAIA and CEPHEUS trials, reinforcing Dara-based regimens as SOC in TIE NDMM regardless of age or frailty. These data offer clinically relevant insights to help guide treatment selection for TIE pts. Clinical trial information: NCT03652064 ; NCT02252172 . PFS, hazard ratio (95% CI) ≥CR rate, % MRD neg with ≥CR (10 -5 ) rate, % Sustained MRD neg with ≥CR (10 -5 ) rate, % Age/ Frailty status MAIA* CEPHEUS** MAIA* CEPHEUS ** MAIA* CEPHEUS** MAIA* CEPHEUS ** <70 y 0.35 (0.21–0.56) 0.60 (0.31–1.18) 56.4 vs 31.2 85.7 vs 68.6 35.9 vs 11.7 74.3 vs 42.9 25.6 vs 3.9 62.9 vs 28.6 70–<75 y 0.64 (0.45–0.89) 0.60 (0.37–0.99) 56.2 vs 31.3 77.9 vs 69.2 36.2 vs 12.2 55.9 vs 47.7 20.8 vs 5.3 45.6 vs 38.5 ≥75 y 0.59 (0.44–0.79) 0.46 (0.22–0.94) 44.4 vs 28.6 80.5 vs 44.4 26.9 vs 9.9 58.5 vs 26.7 13.8 vs 3.1 43.9 vs 15.6 Frail 0.64 (0.48–0.85) 0.62 (0.32–1.18) 44.8 vs 33.1 72.9 vs 54.3 25.6 vs 13.0 56.3 vs 34.3 15.7 vs 4.1 39.6 vs 17.1 Non-frail 0.48 (0.36–0.64) 0.51 (0.34–0.78) 56.6 vs 27.5 84.4 vs 63.6 37.8 vs 9.5 63.5 vs 41.8 21.4 vs 4.0 54.2 vs 32.7 *MAIA: DRd vs Rd; **CEPHEUS: DVRd vs VRd.
Impact of prophylactic cyclophosphamide on ALC and delayed neurotoxicity after cilta-cel.
Tan, Melinda, Schaefers, Christoph, Lim, Kenneth J. C., Chhabra, S, Gertz, MA, Kapoor, Prashant , Kourelis, T., Warsame, Rahma , Cook, Joselle, Bergsagel, Leif P., Wiedmeier-Nutor, Julia Erin, Zanwar, Saurabh , Abdallah, Nadine, Ailawadhi, Sikander, Fonseca, Rafael, Kumar, Shaji, Anastasia, Zekeridou, Lin, Yi, Tan, Melinda Si Yun , Schaefers, Christoph , Lim, Kenneth J C , Chhabra, Saurabh , Parrondo, Ricardo D , Gertz, Morie A. , Kourelis, Taxiarchis , Cook, Joselle , Binder, Moritz , Bergsagel, P. Leif , Abdallah, Nadine , Ailawadhi, Sikander , Fonseca, Rafaël , Kumar, Shaji

Mayo Clinic

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 7543-7543

10.1200/jco.2026.44.16_suppl.7543 Get It

7543 Background: Delayed neurotoxicity (DNT) after ciltacabtagene autoleucel (cilta-cel) is associated with severe morbidity and mortality occurring in 10-15% of patients. A high post-infusion peak absolute lymphocyte count (ALCpeak ≥3x10 9 /L; ALC hi ) is correlated with an increased risk of DNT (25-30%). We previously examined prophylactic dexamethasone (PPX DEX) administered for 3 days when ALC hi was reached and found no reduction in ALC expansion, DNT incidence or severity. Here, we report the use of prophylactic cyclophosphamide (PPX CTX) on ALC kinetics and DNT. Methods: We conducted a retrospective analysis of patients (pts) treated with cilta-cel at Mayo Clinic (09-12/2025; n =60). Pts with ALC hi received CTX 500 mg IV/PO once (n = 22). Outcomes and ALC kinetics including ALCpeak, ALC D28 (ALC D28 ), and area under the curve D1-D28 (ALC AUC ) were compared with PPX DEX cohort (12/2024-08/2025; n =50) and a historical cohort without PPX (04/2022-11/2024; n =116). Results: Pre-lymphodepletion (LD) demographics were similar across historical ALC hi , PPX DEX, and PPX CTX groups. Pre-LD CRP was higher in the historical ALC hi cohort; however, baseline ferritin, CRS, and ICANS, and disease burden did not differ significantly between groups. There were no statistically significant differences in time to ALCpeak or ALC kinetics among the 3 cohorts. Among pts with ALC < 3×10⁹/L treated during the PPX CTX study period, 2 developed cranial nerve palsy (IEC-CNP; 2/38, 5%). Both presented with unilateral facial nerve palsy and were treated with corticosteroids. One pt resolved symptoms by one month, while the second had persistent symptoms at 2 weeks and remains on follow-up. Among ALC hi patients in the PPX CTX cohort, DNT occurred in 4/22 pts (18%), including 1 case of IEC-CNP (5%) and 3 with parkinsonism (IEC-PKS, 14%). Within the PPX CTX cohort, baseline characteristics and post-infusion CRS or laboratory parameters did not differ between patients with and without DNT. Among patients who developed DNT, ALC kinetics were similar across PPX CTX, PPX DEX, and historical cohorts. PPX CTX was well tolerated, with 2 cases of grade 1 nausea reported. The incidence of DNT did not differ significantly between the PPX DEX (14/61, 23%) and PPX CTX (4/22, 18%) cohorts. However, DNT presentations in the PPX CTX cohort appeared milder and were responsive to treatment. Two of three patients (67%) presented with mild symptoms (one with dynamic dysphasia; second with flat affect) that responded to DEX. A third patient presented with typical parkinsonian features (hypomimia, bradykinesia, rigidity) and demonstrated clinical improvement following high-dose CTX. Conclusions: PPX CTX was well tolerated. While it did not significantly impact ALC expansion kinetics or DNT rates, first few cases of IEC-PKS suggest that the presentation may be milder and amenable to less toxic treatment. Larger cohorts are needed to refine optimal prophylactic strategies.
Efficacy and safety of iberdomide, daratumumab, bortezomib, and dexamethasone in patients with newly diagnosed multiple myeloma.
Kapoor, Prashant , Kumar, Shaji, Muchtar, Eli, Gonsalves, Wilson I., Kourelis, Taxiarchis, Buadi, Francis, Asmus, Erik, Larson, Alyssa, Abdallah, Nadine, Zanwar, Saurabh , Cook, Joselle, Dispenzieri, Angela, Warsame, Rahma , Go, Ronald S., Dingli, David, Gertz, MA, Rajkumar, S. Vincent, Knopf, Betsy R., Siddiqui, Mustaqeem Ahmad, Kumar, Shaji , Muchtar, Eli , Gonsalves, Wilson I. , Kourelis, Taxiarchis , Buadi, Francis K. , Asmus, Erik, Abdallah, Nadine , Cook, Joselle , Dispenzieri, Angela , Binder, Moritz , Go, Ronald S. , Dingli, David , Gertz, Morie A. , Siddiqui, Mustaqeem

Mayo Clinic

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 7514-7514

10.1200/jco.2026.44.16_suppl.7514 Get It

7514 Background: Iberdomide (Iber) is a CELMoD that binds with greater specificity & affinity to the cereblon protein of the E3 ligase complex than a traditional IMiD. Both transplant-eligible (TE) & ineligible (TIE) patients (pts) with newly diagnosed multiple myeloma (NDMM) are currently treated with quadruplet induction, consisting of an anti-CD38 monoclonal antibody, a proteasome inhibitor, an IMiD & dexamethasone (dex). We conducted a clinical trial (NCT05392946, IDEAL) to examine the efficacy of a novel finite-duration approach, using Iber, daratumumab, bortezomib & dex (Iber-DVd) quadruplet induction followed by Iber monotherapy maintenance. Methods: Both TE and TIE pts with NDMM were enrolled in this Phase 1 (3+3 design)/Phase 2 (single stage) trial. The primary goal was to assess the ≥complete response (CR) rate — utilizing the more sensitive serum MASS-FIX assay in lieu of serum immunofixation — during induction. Treatment involved twelve 28-day cycles of induction with Iber, given PO at the recommended phase 2 dose (RP2D), days 1-21, daratumumab 1800mg SQ, weekly for 2 cycles, every other week during Cycles 3-6, & every 4 weeks thereafter, bortezomib 1.3 mg/m 2 SQ, weekly & dex 40 mg, weekly, followed by Iber monotherapy (24 cycles). Growth factor was not allowed during the dose-limiting toxicity (DLT) assessment period (Cycle 1). Results: Among 47 pts enrolled, 9 pts were in Phase 1 portion which assessed the maximum tolerated dose (MTD), with Iber starting at 1 mg/day dose, days 1-21 [Dose Level (DL) 1]. DLT (all grade 4 neutropenia) was noted in 3 pts, 2 at DL 1 & 1 at DL -1. This analysis includes 44 pts who received Iber at the RP2D (0.75 mg/day, days 1-21), including 6 pts from the Dose Confirmation Cohort (Phase 1, DL -1), dosed at MTD, & 38 pts in the Dose Expansion Cohort. The median age at registration was 65 years (range 36-86 years), & 23 pts (52.3%) were deemed high-risk. At data cut-off, pts had received a median of 15 cycles (range 3-36) of therapy. Overall response rate was 100%; ≥CR rate, 36.4% (95% CI: 22.4, 52.2) during induction & 52.3% (95% CI: 36.7, 67.5), overall, including the maintenance phase. The marrow flow-based (10 -5 ) MRD negative rate was 29.5% during induction & 47.7% overall. At a median follow-up (FU) 18.3 mos, 2 pts have died (one during FU due to progressive disease & the other on-treatment due to COVID-19). 12- (& 18-) month progression-free survival & overall survival rates were 91% (88%) & 97% (94%), respectively. Most common toxicities at RP2D were lymphopenia, neutropenia (leading 27% of pts to require pegfilgrastim support), rash, peripheral neuropathy, diarrhea, & infections. Cases of high-grade fatigue were low (<5%). Updated data will be presented at the meeting. Conclusions: Iber-DVd is an active and safe regimen for both TE and TIE pts with NDMM, leading to high response rates which improved over time, with nearly one-half of the pts achieving MRD negative state. Clinical trial information: NCT05392946 .
Etentamig in patients (pts) with relapsed/refractory multiple myeloma (RRMM) with prior exposure to B-cell maturation antigen (BCMA)–targeted therapy.
Chhabra, S, Searle, Emma, Popat, Rakesh, Magen, Hila , Gatt, Moshe E., Avivi, Irit, Korde, Neha, Valdes, Cesar Rodriguez , Lichtman, Eben I. , Touzeau, Cyrille, Leleu, Xavier P., Svensson, Anders, Doerr, Thomas, Yu, Jovian , (Lee), Xin (Shane) Li, Ahsan, Aarif, Rosenberg, Tanya, Talati, Chetasi, Kumar, Shaji, Chhabra, Saurabh , Searle, Emma J , Popat, Rakesh , Gatt, Moshe E. , Avivi, I., Baljević, Muhamed , Touzeau, Cyrille , Leleu, Xavier , Svensson, Anders , Doerr, Thomas, Talati, Chetasi , Kumar, Shaji

Mayo Clinic

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 7508-7508

10.1200/jco.2026.44.16_suppl.7508 Get It

7508 Background: Data on response to BCMA-targeted therapies among BCMA-exposed pts with RRMM are limited. Outcomes after sequential/subsequent anti-BCMA bispecific T-cell engagers (Bs-TCE) are vital to evaluate. Etentamig is a next-generation differentiated BCMA x CD3 Bs-TCE composed of a bivalent BCMA-binding domain with a high-avidity, low-affinity CD3-binding domain potentially reducing cytokine release syndrome (CRS), and a silenced Fc tail for extended half-life and convenient monthly (Q4W) dosing. Phase 1 results of etentamig in RRMM showed robust efficacy and potential best-in-class safety. Methods: Arm B of the open-label, Phase 1b MOVISO study (NCT05650632) evaluated etentamig in pts with RRMM with ≥2 prior lines of therapy (PLT), including triple-class and prior BCMA exposure (antibody-drug conjugate [ADC] >30 days or CAR-T >6 months [mo] after last exposure). Primary safety endpoints were CRS and immune effector cell-associated neurotoxicity syndrome (ICANS); efficacy endpoints included objective response rate (ORR; IMWG 2016), duration of response (DoR), and progression-free survival (PFS). Pts received etentamig (60 mg IV; no step-up dosing [SUD]) on Cycle 1 Day 1 and Q4W thereafter. Results: At cutoff (June 11, 2025), 41 prior BCMA-exposed pts (CAR-T, n=24; ADC, n=17) had been treated; 24 (57%) were male, 38 (93%) were White, median (mdn) (range) age was 68 (43–89) years, 37 (88%) had ECOG PS ≤1, and 34 (81%) were triple-class refractory. Mdn (range) PLT was 6 (3–15). For 21 (51%) pts, the last PLT was BCMA directed; 23 (56%) had previously responded to anti-BCMA therapy (17/24 [71%] for CAR-T and 6/17 [35%] for ADC). Mdn (range) time from last prior CAR-T or ADC to first dose of etentamig was 15 (1–30) and 4 (1–45) mo, respectively. Mdn (range) follow-up was 5.5 (0.2–17.1) mo. Despite no SUD, CRS and ICANS were reported in 24 (57%) and 3 (7%) pts, respectively; all G1/2 events, except 1 G3 ICANS. G3/4 neutropenia and infections were reported in 15 (36%) and 17 (41%) pts, respectively. Efficacy outcomes are detailed in the Table (NE, not estimable). For pts whose last PLT was BCMA directed, MRD negativity (clonoSEQ, 10 –5 ) was seen in 2/3 (67%) evaluable pts, along with robust peak activation and proliferation of CD8+ T cells. Conclusions: Pts treated with etentamig achieved durable responses; rates were higher in pts who received CAR-T as last line. No new safety signals were observed; only low-grade CRS was seen despite no SUD. Clinical trial information: NCT05650632 . All prior BCMA (N=41) Prior BCMA CAR-T (N=24) ORR, n/n (%) [95% CI] Overall 17/36 (47) [30–65] 11/22 (50) [28–72] BCMA-directed last PLT 11/19 (58) [34–80] 7/11 (64) [31–89] Mdn DoR, mo [95% CI], No. of pts Overall 13 [7–NE], N=17 13 [7–NE], N=11 BCMA-directed last PLT 13 [7–NE], N=11 13 [7–NE], N=7 Mdn PFS, mo [95% CI], No. of pts Overall 3.4 [3–11], N=41 8.3 [2–NE], N=24 BCMA-directed last PLT 9.4 [2–NE], N=21 9.4 [2–NE], N=12
Prediction of progression in MGUS using transformer-based survival time-series modeling.
Kumbhar, Vaishnavi, Braun, Nicholas, Cook, Joselle, Gonsalves, Wilson I., Buadi, Francis, Hayman, Suzanne R. , Siddiqui, Mustaqeem Ahmad, Kapoor, Prashant , Dispenzieri, Angela, Vachon, C M, Kyle, Robert A., Rajkumar, S. Vincent, Kumar, Shaji, Kumbhar, Vaishnavi, Binder, Moritz , Cook, Joselle , Gonsalves, Wilson I. , Buadi, Francis K. , Siddiqui, Mustaqeem , Dispenzieri, Angela , Kyle, R., Kumar, Shaji

Mayo Clinic

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 7518-7518

10.1200/jco.2026.44.16_suppl.7518 Get It

7518 Background: Monoclonal gammopathy of undetermined significance (MGUS) is common, yet only a minority progress to malignant plasma-cell disorders. Mayo risk stratification uses baseline factors and is commonly implemented/validated in a Cox proportional hazards (CoxPH) framework, which may miss prognostic longitudinal patterns. Methods: We assembled 15,158 MGUS patients with longitudinal laboratory data and progression outcomes (smoldering multiple myeloma, multiple myeloma, AL amyloidosis, or Waldenström macroglobulinemia). We compared a Mayo-factor Cox proportional hazards (CoxPH) baseline versus STRaTS, a transformer-based survival model, to predict progression risk at 3-, 5-, and 10-year horizons. STRaTS leveraged longitudinal trajectories of routine labs including hemoglobin, platelets, differential counts (neutrophils/lymphocytes/monocytes), immunoglobulins (IgG/IgA/IgM), free light chains (kappa/lambda), M-spike, and creatinine. To minimize bias, we used laboratory results collected from 1–3 years after diagnosis and started follow-up at year 3; patients progressing before year 3 or lacking follow-up beyond year 3 were excluded. A total of 7,305 patients met eligibility and were split into train/validation/test cohorts of 4,383/1,461/1,461. Discrimination was assessed by concordance index (C-index). Clinical operating performance was evaluated on a held-out test cohort by comparing sensitivity and specificity at the same proportion of patients selected for intensified surveillance (same workload). Results: Among MGUS patients with complete baseline Mayo factors(N=3,388), Kaplan–Meier–estimated 3-/5-/10-year cumulative progression risk was 0.1/0.4/3.4% (Low), 3.0/4.3/7.9% (Low-Intermediate), 4.4/6.4/14.1% (High-Intermediate), and 8.9/12.5/16.9% (High). On a held-out test cohort, STRaTS demonstrated superior discrimination versus the Mayo-factor CoxPH (C-index 0.75 vs 0.538; p<0.0001). Both models were trained and evaluated on identical train/test splits. At the same surveillance workload, STRaTS achieved higher sensitivity with comparable specificity; when 40.3% of patients were selected for closer surveillance, 3-year sensitivity was 81.0% for STRaTS versus 47.6% for CoxPH (Table). Conclusions: Among MGUS patients who remain progression-free at 3 years, transformer-based survival modeling of longitudinal laboratory trajectories provides more accurate individualized conditional progression risk estimates and improved workload-matched identification of progressors compared with the conventional Mayo/Cox approach. Sensitivity/specificity (%). Operating Point Flagged % STRaTS Sens / Spec (%) CoxPH Sens / Spec (%) Int+High, 3y 40.3 81.0 / 58.5 47.6 / 58.9 Int+High, 5y 40.3 81.2 / 60.4 46.9 / 58.8 Int+High, 10y 40.3 25.0 / 56.3 23.8 / 58.7 Two-Group High (≥2 factors), 5y 5.6 37.4 / 93.4 35.4 / 93.1
Earlier CRS identification with continuous wearable monitoring in outpatient CAR T-cell therapy.
Paludo, Jonas, Pettinati, Michael, Guo, Christine, Ruff, Michael W. , Holmes, Lucy , Haugen, Kelsey L., Amundson, Michelle, Khurana, Arushi , Bennani, Nabila Nora, Wang, Yucai, Kourelis, T., Kumar, Shaji, Kapoor, Prashant , Abdallah, Nadine, Ansell, Stephen M., Haddad, Tufia C. , Lin, Yi, Paludo, Jonas , Pettinati, Michael J. , Pritchett, Joshua C. , Holmes, Lucy M., Haugen, Kelsey, Kourelis, Taxiarchis , Kumar, Shaji , Binder, Moritz , Abdallah, Nadine , Ansell, Stephen M. , Routman, David M.

Mayo Clinic

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 1633-1633

10.1200/jco.2026.44.16_suppl.1633 Get It

1633 Background: CAR-T cell therapy has transformed outcomes of hematologic malignancies and is poised to expand into solid malignancies. However, broader use of CAR-T remains constrained by the need for timely cytokine release syndrome (CRS) detection. Current episodic monitoring may miss early physiologic changes. Wearable digital health technologies (DHTs), offering continuous monitoring and real-time alerts, could enable earlier CRS detection, further support outpatient delivery, and expand access to CAR-T and potentially other immunotherapies associated with CRS. Methods: This single-center observational study (NCT05018208) enrolled patients receiving FDA-approved CAR-T products in the outpatient setting at Mayo Clinic, Rochester MN. Management of post-CAR-T complications (e.g. CRS) followed the institution’s standard of care. Patients were monitored from day -5 to day +30 post infusion with intermittent remote patient monitoring (SoC) and an arm-worn wearable device for continuous monitoring (DHT). Patients were included in this analysis if DHT data were available for ≥ 5h of data/day or ≥ 2h of data/night on ≥2 days or nights for baseline and ≥1 day or night within 72h prior to CRS, or at least 2h within 4h of CRS onset, or if DHT was available for ≥7 days/nights post infusion with no CRS event. CRS detection time by DHT was defined as the onset of pyrexia or threshold-based deviation from an individual’s baseline pulse distributions. Results: 32 patients were included in this report (median age 64 years, gender 12 F/20 M, diagnoses 18 MM/14 NHL). 25 patients experienced a CRS event, with maximum CRS grades ranging from 1-3 (16 G1, 8 G2, 1 G3). 24/25 patients with CRS required tocilizumab/steroid. Median CRS onset time was 3.4 days (range 0.4-18.4). 12/32 patients had sufficient DHT data (7 CRS, 5 no CRS) for analysis. 5 patients with CRS had a DHT detection time in advance of the SoC by a median of 13h (range 2.8 - 69.2). The DHT prediction of CRS by baseline HR change was earlier than the first episodic fever by a median of 14.5h (range 13-77.5). The remaining 2/7 patients who did not have CRS detected by the DHT had missing DHT data for more than 45h before a treated CRS event. DHT detected CRS in 2/5 patients without CRS according to SoC. One patient had fever caught with intermittent monitoring. The other was treated for neutropenia fever with suspicion of CRS and/or infection. Conclusions: These results offer evidence that continuous DHT can identify CRS events earlier than intermittent monitoring (SoC). Despite limitations related to compliance with wearable device use and data missingness, and variability in clinical management of CRS, we highlight the usability of DHT and its potential for future studies with optimized strategies to address these limitations. Clinical trial information: NCT05018208 .
Treatment of Multiple Myeloma: ASCO Living Guideline, Version 2026.1.1
Banerjee, Rahul , Cheung, Matthew C. , Derman, Benjamin, Messersmith, Hans , Bhella, Sita, Chmielewski, Cynthia, Ebraheem, Mohammad, Kennedy, C. Todd , Kumar, Shaji , Langerak, Alan, Mian, Hira , Seth, Rahul, Subramanian, Latha, Wildes, Tanya M., Zanwar, Saurabh , Zhuo, Ying, Derman, Benjamin A , Al Hadidi, Samer , Ebraheem, Mohammad S , Kennedy, C Todd , Kumar, Shaji K , Lipe, Brea , Mian, Hira , Riva, Eloisa , Usmani, Saad , Wildes, Tanya , Zanwar, Saurabh S , Hicks, Lisa K. , Messersmith, Hans , Banerjee, Rahul , Derman, Benjamin A. , Chmielewski, Cynthia, Langerak, Alan, Seth, Rahul, Usmani, Saad Z. , Wildes, Tanya M.

Mayo Clinic

Journal of Clinical Oncology | May 20, 2026 | Volume: 44 | Issue: 22 | Pages: No page available

10.1200/jco-26-01139 | PMID 42160714 Get It

This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 ). Updates are published regularly and can be found on the ASCO Publications website .
Predictors of renal response in AL amyloidosis following anti‐plasma cell therapy: The impact of baseline serum free light chain levels and light chain isotype
Rees, Matthew J., Yohannan, Binoy, Geyer, Susan M. , Atallah‐Yunes, Suheil Albert , Toumeh, Nadia , Gertz, MA, Dispenzieri, Angela, Leung, Nelson , Hayman, Suzanne, Buadi, Francis, Dingli, David, Warsame, Rahma, Kapoor, Prashant , Kourelis, Taxiarchis, Gonsalves, Wilson, Kumar, Shaji, Gertz, Morie A. , Geyer, Susan , Gertz, Morie A , Cook, Joselle M , Rajkumar, S Vincent , Muchtar, E , Leung, Nelson , Atallah-Yunes, Albert , Rees, Matthew J. , Yohannan, Binoy, Dispenzieri, Angela , Hayman, S., Buadi, Francis K. , Cook, Joselle , Dingli, David , Warsame, Rahma , Binder, Moritz , Kourelis, Taxiarchis , Gonsalves, Wilson I. , Rajkumar, S. Vincent , Kumar, Shaji , Muchtar, Eli

Mayo Clinic

British Journal of Haematology | May 11, 2026 | Volume: 209 | Issue: 1 | Pages: 149-159

10.1111/bjh.70542 | PMID 42108212 Get It

Summary Renal response (RenR) in light‐chain (AL) amyloidosis is associated with a lower risk of end‐stage kidney disease and improved survival. However, substantial variation exists in the time to and depth of RenR. We investigated variables associated with RenR in a retrospective study of newly diagnosed AL amyloidosis patients ( n = 350) assessable for RenR between 2010 and 2022. RenRs were recorded at 6, 12 and 24 months and best response. Deep RenR was defined as a ≥renal very good partial response (RenVGPR, >60% reduction in 24‐h proteinuria or ≤200 mg). Logistic regression and competing risk methods were used to examine variables associated with RenR. The median age was 64 years, and median follow‐up was 5.5 years. On multivariable logistic regression, obtaining ≥HemVGPR within 6 months, kappa isotype, high baseline difference between involved and uninvolved free light chains (dFLC ≥40 mg/dL), renal stage and autologous haematopoietic stem cell transplant (AHSCT) were significantly associated with deep RenR. Cumulative incidence rates for deep RenR, treating death or renal progression as a competing event, demonstrated that early HemR, first‐line AHSCT, lower renal stage and dFLC ≥40 mg/dL significantly increased the likelihood of deep RenR. Specific clonal plasma cell features, namely light‐chain isotype and baseline dFLC levels, independently influence the timing and depth of RenRs in AL amyloidosis following treatment, in addition to renal stage and HemR.
Infections in patients receiving daratumumab for newly diagnosed multiple myeloma: a pooled analysis of MAIA and ALCYONE
Bahlis, Nizar J. , Facon, Thierry, San-Miguel, Jesus, Usmani, Saad Z., Dimopoulos, Meletios-Athanasios A., Moreau, Philippe, Manier, Salomon , NS, Raje, Orlowski, Robert Z. , Goldschmidt, H, Hulin, Cyrille, Weisel, K, Leleu, Xavier, Plesner, Torben , Jakubowiak, Andrzej J, Cook, Gordon, Quach, H, Venner, Christopher P., Cavo, M, Ngo, Mai, Bolyard, Kasey, Carson, R, Borgsten, Fredrik, Mateos, María‐Victoria , Kumar, Shaji , Miguel, Jesús F. San , Bahlis, Nizar Jacques , San-Miguel, Jesus , Zweegman, Sonja , Perrot, Aurore , Manier, Salomon , Orlowski, Robert Z. , Goldschmidt, Hartmut , Mohty, Mohamad , Leleu, Xavier , Cook, Gordon , Quach, Hang , Mateos, María-Victoria , Kumar, Shaji K , Facon, Thierry T.F. , Usmani, Saad Z. , Dimopoulos, Meletios A , Moreau, Philippe , Chari, Ajai , Goldschmidt, Hartmut , Basu, Supratik , Hulin, Cyrille , Weisel, Katja C , Mohty, Mohamad , Leleu, Xavier , Jakubowiak, Andrzej , Cook, Gordon , Quach, Hang , Cavo, M., Carson, Robin

Mayo Clinic

Blood Advances | May 5, 2026 | Volume: 10 | Issue: 13 | Pages: 4541-4550

10.1182/bloodadvances.2025019323 | PMID 42085642 Get It

Abstract Both the phase 3 MAIA and ALCYONE studies demonstrated significant survival benefit with the addition of daratumumab to standard-of-care Rd (Revlimid [lenalidomide] and dexamethasone; D-Rd) or to VMP (Velcade [bortezomib], melphalan, and prednisone; D-VMP), respectively, vs Rd or VMP alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). Patients with NDMM are highly susceptible to infection; therefore, gaining a greater understanding of infection incidence may help to mitigate future risk. We conducted a pooled analysis of infection incidence, timing, and management strategies from MAIA and ALCYONE. The median (range) age of the pooled population was 72 (40-93) years. Incidence was higher with D-Rd/D-VMP vs Rd/VMP for grade 3/4 (36.9% vs 22.4%) and grade 5 (3.0% vs 1.5%) infections; however, exposure-adjusted incidence rates were generally comparable between groups. Any-grade infections led to the discontinuation of study treatment in ∼2% of patients across treatment groups. Of the timing intervals explored, the highest incidence of grade 3/4 infection occurred within the first 6-month interval of study treatment initiation in both groups. Median time to the first onset of grade 3/4 infections (per Kaplan-Meier estimates) was 83.3 months and not estimable in the D-Rd/D-VMP and Rd/VMP groups, respectively. Although the rates of D-Rd/D-VMP treatment discontinuation due to infection remained low in MAIA and ALCYONE, clinicians should remain vigilant about infections throughout treatment and follow local guidelines and International Myeloma Working Group recommendations to minimize the risk of infection. These trials were registered at www.ClinicalTrials.gov as NCT02252172 (MAIA) and NCT02195479 (ALCYONE).