Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA

Panelists discuss how venetoclax management requires standardized approaches to duration, bone marrow biopsy timing, growth factor use, and azole antifungal selection, with practices varying significantly between centers and the need for consistent protocols to optimize patient outcomes.

Panelists discuss how IDH inhibitors, particularly ivosidenib combined with azacitidine, represent potentially the greatest advance in AML treatment due to significant overall survival improvements, though adoption challenges include waiting for mutation results and limited patient applicability.

Panelists discuss how the treatment landscape has evolved from limited options to include hypomethylating agents and venetoclax combinations, with emerging oral formulations promising greater accessibility while requiring careful consideration of patient selection and toxicity management.

Panelists discuss how combination trials like VIALE-A and VIALE-C have demonstrated venetoclax’s survival benefits when added to hypomethylating agents, opening doors for numerous combination studies while emphasizing the need for randomized trials to prove clinical benefit in different disease contexts.

Panelists discuss how venetoclax has revolutionized AML treatment by providing effective therapy options for older patients with previously untreatable disease, enabling higher response rates, longer survival, and increased transplant eligibility while transforming the treatment landscape across all age groups.

Panelists discuss how transplant eligibility has expanded beyond traditional intensive chemotherapy candidates to include patients receiving lower intensity regimens, with earlier transplant consultations and consideration of organ function preservation through less toxic induction approaches.

Panelists discuss how current NCCN guidelines emphasize the importance of treating AML at experienced centers with proper infrastructure, while treatment decisions are based on intensive vs nonintensive therapy eligibility and specific genetic mutations like FLT3, IDH1, and TP53.

Panelists discuss how social determinants of health significantly impact AML care, particularly regarding transportation access, health literacy, and the intensive nature of treatment requiring frequent clinic visits for blood work and transfusions, which disproportionately affects patients living far from treatment centers.

Panelists discuss how the greatest unmet needs include addressing poor outcomes in specific subsets like TP53-mutant disease, managing the increasingly older population with secondary mutations, and ensuring global access to targeted therapies and next-generation sequencing.

Panelists discuss how fitness assessment has evolved beyond traditional age cutoffs to incorporate comprehensive geriatric assessments, frailty measures, and individualized evaluations, while questioning whether intensive therapy should automatically be given to fit patients given newer effective treatment options.

Panelists discuss how current risk stratification systems, particularly the European Leukemia Net 2022 classification for intensive therapy and the 2024 classification for lower intensity treatments, categorize patients based on complex cytogenetics and molecular features to guide prognosis and treatment selection.

Panelists discuss how the pathophysiology of acute myeloid leukemia has evolved from a single phenotype understanding to recognizing diverse genetic events that lead to transformation at the hematopoietic stem cell level, with treatment decisions now increasingly integrated with specific genetic mutations despite the disease’s rapid progression timeline.

Panelists discuss how upcoming ASCO presentations will focus on long-term CAR T-cell therapy outcomes showing potential cure plateaus, minimal residual disease (MRD)–guided treatment escalation/de-escalation strategies, tri-specific antibodies, and the economic value of using MRD negativity to guide maintenance therapy discontinuation decisions.

Panelists discuss how recent updates from the phase 3 IsKia trial demonstrate that isatuximab combined with carfilzomib, lenalidomide, and dexamethasone improves minimal residual disease negativity rates by approximately 10% at both the 10–5 and 10–6 levels, particularly benefiting high-risk patients.

Panelists discuss how the PERSEUS trial’s subgroup analysis reinforced that sustained minimal residual disease negativity predicts better long-term outcomes and demonstrated the potential for treatment de-escalation at the 2-year mark, while other trials like Advance showed dramatic increases in MRD negativity rates with quadruplet therapy.

Panelists discuss how emerging evidence from first-line therapy trials continues to demonstrate the superiority of quadruplet over triplet regimens, with the CEPHEUS subgroup analysis confirming that even higher-risk and less-fit patients can benefit from 4-drug combinations while maintaining acceptable safety profiles.

Panelists discuss how quality of life (QOL) and treatment convenience should be balanced with maximal depth of response through personalized therapy approaches, emphasizing the importance of multidisciplinary care teams and the flexibility to adapt treatment regimens based on individual patient preferences and circumstances.

Panelists discuss how newer immune-based therapies and bispecific antibodies may enable fixed-duration treatment approaches that could eliminate the need for stem cell transplant in older but fit patients, potentially allowing for treatment-free intervals after achieving deep responses.

Panelists discuss how to balance achieving deeper MRD-negative responses against increased toxicity risks in transplant-ineligible patients by personalizing therapy through dose modifications, weekly vs twice-weekly dosing schedules, and careful monitoring while maintaining treatment intensity similar to clinical trials.

Panelists discuss how NCCN guidelines are expected to incorporate quadruplet-based regimens as reasonable treatment approaches for transplant-ineligible patients, while emphasizing the need for personalized treatment strategies that consider individual patient frailty and high-risk genetics rather than applying uniform approaches across all older patients.

Panelists discuss how the CEPHEUS trial demonstrated that quadruplet therapy (daratumumab, bortezomib, lenalidomide, and dexamethasone) significantly improved minimal residual disease negativity rates compared to triplet therapy in transplant-ineligible multiple myeloma patients, achieving approximately 60% vs 47% 10–5 responses while maintaining manageable safety profiles.

Panelists discuss how emerging therapies like CAR T cells and bispecific antibodies may transform frontline treatment by potentially replacing transplant or changing induction regimens, while considering the cost implications and need for sustainable care models.

Panelists discuss how early relapse in standard-risk patients represents a failure of current risk assessment methods and may require advanced sequencing technologies to identify hidden high-risk features that traditional fluorescence in situ hybridization testing misses.

Panelists discuss how autologous stem cell transplant (ASCT) deferral should be approached cautiously with concrete medical reasons, as transplant continues to provide superior progression-free survival and potentially curative outcomes for a subset of patients.

Panelists discuss how maintenance therapy should be tailored based on risk profiles, with standard-risk patients receiving single-agent lenalidomide while high-risk patients may benefit from combination maintenance strategies to achieve more durable responses.

Panelists discuss how minimal residual disease (MRD) status can guide post-transplant treatment decisions, particularly for high-risk patients who don’t achieve MRD negativity and patients considering discontinuation of long-term maintenance therapy.

Panelists discuss how quadruplet regimens show improved efficacy over triplet regimens without significantly increased safety concerns, with anti-CD38 antibodies being well tolerated and NCCN guidelines now recommending 4-drug regimens for transplant-eligible patients.

Panelists discuss how treatment strategies differ between transplant-eligible and transplant-ineligible multiple myeloma patients, with transplant eligibility determined by functional status rather than age alone, and how quadruple therapy regimens are increasingly used for transplant-eligible patients to achieve deep, durable responses.

Panelists discuss how autologous stem cell transplant remains essential in frontline multiple myeloma management despite improved quadruple therapy outcomes, emphasizing that current evidence still supports transplantation for eligible patients rather than deferring it.

Medical experts offer their insights and closing remarks regarding patient feedback for MDS.