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The International Academy for Clinical Hematology (IACH) is a global, non-profit educational organization dedicated to advancing excellence, equity, and innovation in clinical hematology. Since its creation, the IACH has built an international community spanning more than 130 countries, leveraging digital-first education, scientific collaboration, and professional networking to improve patient care worldwide. This document presents the IACH Strategic Vision for 2026–2030, outlining a structured roadmap for the Academy’s next phase of growth and international leadership. The strategy is built upon six interdependent pillars: scientific excellence and credibility; digital leadership and intelligent learning; academic alliances and global footprint; innovation, visibility, and advocacy; transparency and sustainability; and brand positioning with global impact. By reinforcing scientific rigor, embracing digital transformation, and promoting innovation, the IACH aims to become the most trusted global reference for clinical hematology education and collaboration. This strategic vision positions the IACH as a unifying platform to unite the world hematology community under one banner of knowledge, collaboration, and compassion, for the benefit of every patient, everywhere.

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.

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).

ABSTRACTObjectivesThis final post hoc analysis evaluated patient‐reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D‐Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5‐month follow‐up in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.MethodsKey scales from the EORTC QLQ‐C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.ResultsThe intent‐to‐treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D‐Rd‐treated patients showed improvements from baseline that were sustained over 5 years in the intent‐to‐treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D‐Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16–2.91]), physical functioning (1.93 [1.18–3.14]), pain (1.41 [0.90–2.22]), and fatigue (2.00 [1.24–3.23]). Greater proportions of patients with bone lesions improved with D‐Rd versus Rd on GHS and physical functioning.ConclusionsIn transplant‐ineligible patients with NDMM, D‐Rd improved health‐related quality of life over a 5‐year period versus Rd. Trial Registration: ClinicalTrials.gov: NCT02252172

AbstractDeeper responses are associated with longer survival in multiple myeloma (MM); however, limited data exist on the impact of response kinetics on outcomes. We investigated progression‐free survival (PFS) and duration of response (DOR) by response depth and in early (best confirmed response 0–4 months; n = 424) versus late responders (best confirmed response >4 months; n = 281). Newly diagnosed patients enrolled in TOURMALINE‐MM2 receiving ixazomib‐lenalidomide‐dexamethasone (IRd) (n = 351) or placebo‐Rd (n = 354) were evaluated post hoc. Deeper responses were associated with longer PFS (complete response [CR] not reached [NR], very good partial response [VGPR] 37.2 months, partial response [PR] 16.4 months) and DOR (CR NR, VGPR 42.6 months, PR 15.4 months). Among patients with a PFS (n = 511) or DOR (n = 484) of ≥6 months who achieved ≥PR, median PFS was prolonged among late versus early responders receiving IRd (59.7 vs. 17.9 months) or placebo‐Rd (56.6 vs. 12.4 months), as was median DOR (IRd, NR vs. 20.9 months; placebo‐Rd, 58.2 vs. 11.7 months). While the treatment paradigm for newly diagnosed MM is treatment to progression, our findings suggest slowness of response to a proteasome inhibitor‐immunomodulatory drug‐steroid combination is not a negative predictor of outcome.

8037 Background: Both daratumumab in combination with lenalidomide and dexamethasone (DRd) and bortezomib in combination with lenalidomide and dexamethasone (VRd) are endorsed by NCCN guidelines as preferred regimens for the treatment of transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). DRd and VRd have each demonstrated superior efficacy relative to lenalidomide and dexamethasone (Rd) alone in the MAIA and SWOG S0777 trials, respectively, but have not been compared directly in a head-to-head trial. Naive comparisons of efficacy across the 2 trials may be biased because MAIA enrolled only TIE patients (median age 73 years), whereas S0777 enrolled a mixed transplant-not-intended (TNI) population, which included both TIE patients and patients choosing to defer/refuse frontline stem cell transplantation (median age 63 years). Methods: The present study leveraged individual patient-level data (IPD) from both trials to perform an anchored indirect treatment comparison of DRd vs VRd, adjusting for differences in trial eligibility criteria and baseline patient characteristics. Harmonized inclusion criteria (NDMM, age ≥65 years, ECOG performance status ≤2) were applied to both trial populations. Age ≥65 years served as a proxy for TIE status since S0777 enrolled a mixed TNI population. Propensity score (PS) reweighting was used to balance the 2 trial populations on key baseline prognostic factors including age, sex, ISS stage, ECOG performance status, hemoglobin, eGFR, lactate dehydrogenase (LDH) level, and cytogenetic risk. Missing data were addressed with multiple imputation. After alignment of inclusion criteria and PS reweighting, an anchored indirect comparison was performed wherein within-trial progression-free survival (PFS) hazard ratios (HRs) for DRd vs Rd and VRd vs Rd were estimated and used to make indirect inference about PFS for DRd vs VRd. Results: 727 MAIA participants and 198 S0777 participants were eligible for inclusion. After PS reweighting, the trial populations were balanced on the key baseline prognostic factors identified above (standardized difference < 0.1 for each). The adjusted PFS HRs were 0.53 (95% CI: 0.41–0.68; P< 0.0001) for DRd vs Rd in MAIA and 0.88 (0.63–1.23; P= 0.46) for VRd vs Rd in S0777. In the adjusted Rd-anchored indirect comparison, the PFS HR for DRd vs VRd was 0.60 (0.39–0.90; P= 0.02). Conclusions: In this adjusted indirect treatment comparison based on IPD from the MAIA and S0777 trials, PFS was significantly longer for DRd relative to VRd. In the absence of a head-to-head trial comparing DRd and VRd, the present study may help to inform treatment selection in TIE patients with NDMM.

Abstract Background Because patients with newly diagnosed multiple myeloma (NDMM) do not always receive any treatment beyond first-line (1L) therapy, it is imperative that patients receive the best treatment in the 1L setting. However, the optimal initial treatment remains to be identified. We performed a clinical simulation to assess potential outcomes with different treatment sequences. Patients and Methods We used a partitioned survival model to compare overall survival (OS) with (1) daratumumab, lenalidomide, and dexamethasone (D-Rd) in 1L followed by a pomalidomide- or carfilzomib-based regimen in second line (2L) versus (2) bortezomib, lenalidomide, and dexamethasone (VRd) in 1L followed by a daratumumab-based regimen in 2L versus (3) lenalidomide and dexamethasone (Rd) in 1L followed by a daratumumab-based regimen in 2L. Probabilities of transition between health states (1L, 2L+, and death) were based on published clinical data and real-world data from the Flatiron Health database. The proportion of patients discontinuing treatment after 1L (attrition rates) in the base case was estimated with a binomial logistic model using data from the MAIA trial. Results Using D-Rd in 1L conferred a longer median OS compared with delaying daratumumab-based regimens until 2L after VRd or Rd, respectively (8.9 [95% CrI 7.58-10.42] vs. 6.92 [5.92-8.33] or 5.75 [4.50-7.25] years). Results of scenario analyses were consistent with the base case. Conclusion Our simulation, which incorporates clinically representative treatments and attrition rates, supports the use of D-Rd as initial therapy, rather than delaying the use of daratumumab until later lines of therapy, in patients with transplant-ineligible NDMM.