Poll Results Reveal Readers’ Top Abstracts at ASH 2025

With the 2025 American Society of Hematology (ASH) Meeting & Exposition kicking off on Saturday, December 6, in Orlando, Florida, Targeted Oncology is bringing you background on the most exciting abstracts across hematologic malignancies set to be presented.

Targeted Oncology conducted polls on X and LinkedIn to identify which multiple myeloma, chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and myelofibrosis abstracts specialists were most anticipating. See the results of our polls below.

What Are the Top Abstracts to Watch in Multiple Myeloma at the ASH 2025 Meeting?

Poll 1: Which of these myeloma abstracts are you most anticipating at ASH 2025?

The MajesTEC-3 captured the most votes on X and tied for first place on LinkedIn.

The phase 3 MajesTEC-3 study evaluated the bispecific antibody teclistamab (Tecvayli) combined with daratumumab (Darzalex; Tec-Dara) vs standard-of-care (SOC) triplets in patients with relapsed/refractory (R/R) multiple myeloma who had 1 to 3 prior lines of therapy.¹

The Tec-Dara regimen demonstrated a statistically and clinically significant improvement in the primary end point of progression-free survival (PFS; median PFS not reached vs 18.1 months; HR, 0.17; P <.0001). Significantly, higher rates of overall response, complete response, and MRD negativity were also observed. Crucially, overall survival (OS) was also significantly favored with Tec-Dara (HR, 0.46; P <.0001). The 36-month PFS rate was 83.4% for Tec-Dara vs 29.7% for SOC. Safety profiles were manageable, with infections being the most notable difference, which were mitigated by prophylaxis and less frequent dosing over time. The study concludes that Tec-Dara should be a new standard of care for R/R myeloma as early as first relapse.

Presentation Details: Tuesday, December 9, at 8:45am ET

What Are the Top Abstracts to Watch in CLL at the ASH 2025 Meeting?

Poll 2: Which of these CLL abstracts are you most anticipating at ASH 2025?

Results were split between platforms, with the phase 2 study of lisaftoclax following BTK failure taking the top spot on X, while the head-to-head comparison of pirtobrutinib (Jaypirca) and ibrutinib (Imbruvica) won on LinkedIn.

A pivotal phase 2 study investigated lisaftoclax, a novel BCL2 inhibitor, in 77 patients with R/R CLL/small lymphocytic lymphoma (SLL) who had failed prior BTK inhibitor therapy and presented with either prior immunochemotherapy failure or high-risk factors.² With a median follow-up of 22 months, lisaftoclax monotherapy achieved a significant objective response rate (ORR) of 62.5%. The median PFS was 23.89 months, and the median duration of response (DOR) was 18.53 months, despite a high proportion of patients having high-risk factors like del(17p)/TP53 mutations and complex karyotype. The safety profile was acceptable, with common grade ≥3 adverse events being hematologic (neutropenia, thrombocytopenia). Lisaftoclax demonstrated high efficacy in this heavily pretreated, high-unmet-need population.

Presentation Details: Saturday, December 6, at 10:15am ET

Additionally, the first head-to-head comparison randomized 662 BTK inhibitor-naive patients with CLL/SLL to receive either the noncovalent pirtobrutinib or covalent ibrutinib.³

The study met its primary end point, demonstrating the noninferiority of the ORR for pirtobrutinib vs ibrutinib in both the intent-to-treat (ITT) and R/R populations (P <.0001). The ORR for pirtobrutinib was 87.0% in the ITT population compared with 78.6% for ibrutinib. Though not yet mature, PFS favored pirtobrutinib, particularly in the treatment-naive setting (HR, 0.24). Importantly, pirtobrutinib showed a lower incidence of cardiovascular adverse events, like atrial fibrillation/flutter (2.4% vs 13.5%), suggesting a favorable safety profile compared with ibrutinib.

Presentation details: Sunday, December 7, at 5:30pm ET

What Are the Top Abstracts to Watch in Myelofibrosis and AML at the ASH 2025 Meeting?

Poll 3: Which of these myelofibrosis and AML abstracts are you most anticipating at ASH 2025?

The phase 1 study of CLN-049 was the top pick on X. CLN-049, a novel humanized bispecific T-cell engager targeting FLT3 (on blasts) and CD3 (on T cells), was evaluated in a phase 1 study for patients with R/R AML and MDS.⁴ The agent demonstrated an acceptable safety profile across 40 patients, with all cytokine release syndrome events being grade 1 or 2, and no treatment-related deaths. Antileukemic activity was observed at the target dose in 23 evaluable patients with AML, yielding a composite CR rate of 30% and an ORR of 57%. Notably, the highest dose tested resulted in a 69% ORR. Responses were seen even in poor-prognosis TP53-mutated AML, highlighting CLN-049's potential as an off-the-shelf immunotherapy in this heavily pretreated population.

Presentation Details: Monday, December 8, at 10:45am ET

On LinkedIn, MANIFEST-2 was the abstract attracting the most attention. The phase 3 study is reporting updated 96-week results on pelabresib, a BET inhibitor, combined with the JAK inhibitor ruxolitinib (Jakafi) vs ruxolitinib monotherapy in JAK inhibitor-naive patients with myelofibrosis.⁵

The combination demonstrated sustained and durable benefits in patients remaining on treatment. At week 96, a spleen volume reduction of ≥ 35% (SVR35) was observed in 91.5% of evaluable patients in the combination arm, significantly higher than the 57.5% in the monotherapy arm. Furthermore, the combination showed greater improvement in symptoms (TSS50, 36.9% vs 28.2%) and achieved a higher dual SVR35/TSS50 response (31.8% vs 15.7%). The combination had a similar overall safety profile to ruxolitinib alone and showed a numerical trend toward fewer deaths and progression events, suggesting a clinically meaningful benefit and potential for disease modification.

Presentation Details: Monday, December 8, at 3:30pm ET

What Are the Top Abstracts to Watch in Other Hematologic Malignancies at the ASH 2025 Meeting?

Poll 4: Which of these abstracts in other hematologic malignancies are you most anticipating at ASH 2025?

VAYHIT2 was the top choice on both LinkedIn and X. The phase 3 VAYHIT2 study investigated adding the novel anti-BAFF receptor antibody, ianalumab, to eltrombopag in adult patients with newly diagnosed primary immune thrombocytopenia (ITP) who had an insufficient response to first-line corticosteroids.⁶

Both ianalumab doses (9 mg/kg and 3 mg/kg) significantly prolonged the time to treatment failure (TTF) compared to placebo plus eltrombopag (median TTF, 13.0 months and not estimable vs 4.7 months). The combination also resulted in a significantly higher rate of stable response at 6 months (SR6) in the 9 mg/kg arm (62.0% vs 39.2%). Ianalumab was well-tolerated, with no increased risk of infection observed. The results suggest that early intervention with ianalumab provides deep, durable responses, reduces fatigue, and may offer a disease-modifying effect in ITP.

Presentation Details: Tuesday, December 9, at 7:45am ET

REFERENCES

1. Mateos MV, Bahlis N, Perrrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3. Presented at: 2025 ASH Meeting & Exposition; December 6–9, 2025; Orlando, Florida. Abstract LBA-6.

2. Zhou K, Wang T, Zheng M, et al. Results of a registrational Phase 2 study of lisaftoclax monotherapy for treatment of patients (pts) with Relapsed/Refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who had failed Bruton’s tyrosine kinase inhibitors (BTKis). Presented at: 2025 ASH Meeting & Exposition; December 6–9, 2025; Orlando, Florida. Abstract 88.

3. Woyach J, Qui L, Grosicki S, et al. Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor. Presented at: 2025 ASH Meeting & Exposition; December 6–9, 2025; Orlando, Florida. Abstract 683.

4. Abdul-Hay M, Vale C, Chan O, et al. Preliminary anti-leukemia activity from A phase 1 study of cln-049, a novel anti-FLT3 x antiCD3 bispecific T-cell engager, in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and myelodysplastic syndrome (MDS). Presented at: 2025 ASH Meeting & Exposition; December 6–9, 2025; Orlando, Florida. Abstract 768.

5. Rampal R, Mascarenhas J, Grosicki S, et al. Durable efficacy and long-term safety with pelabresib plus ruxolitinib in JAK Inhibitor Naive myelofibrosis: 96-week Results from the Phase III MANIFEST-2 study. Presented at: 2025 ASH Meeting & Exposition; December 6–9, 2025; Orlando, Florida. Abstract 910.

6. Al-Samkari H, Cuker A, Zaja F, et al. Primary results from VAYHIT2, a randomized, double-blind, phase 3 trial of ianalumab plus eltrombopag versus placebo plus eltrombopag in patients with primary immune thrombocytopenia (ITP) who failed first-line corticosteroid treatment. Presented at: 2025 ASH Meeting & Exposition; December 6–9, 2025; Orlando, Florida. Abstract LBA-2.