Evolving Treatment Strategies Reshape the Landscape of Hematologic Malignancies

From JAK inhibitors in polycythemia vera and myelofibrosis to treatment updates in follicular lymphoma and large B-cell lymphoma (LBCL), recent data and real-world experience are shaping how oncologists approach treatment selection in clinical practice, according to Naseema Gangat, MBBS.

In an interview with OncLive® following a State of the Science Summit™ on hematologic malignancies, Gangat, who chaired the event, detailed unmet needs regarding JAK inhibitors in polycythemia vera and myelofibrosis, 2025 updates in the follicular lymphoma landscape, and the roles of axicabtagene ciloleucel (axi-cel; Yescarta) and lisocabtagene maraleucel (liso-cel; Breyanzi) in the treatment of patients with LBCL.

In another article, Gangat discussed the role of ruxolitinib as standard of care for the management of polycythemia vera and myelofibrosis.

Gangat is a professor of medicine and consultant in hematology at Mayo Clinic in Rochester, Minnesota.

OncLive:What questions still need to be addressed regarding JAK inhibitors in polycythemia vera or myelofibrosis?

Gangat: The long-term safety [profile of ruxolitinib (Jakafi) needs to be addressed]. JAK inhibitors reduce cell-mediated immunity, so there is a small risk for opportunistic infections. We always have our patients vaccinated against shingles, especially our older patients. However, those are some [aspects] that need to be addressed, especially [because] the thrombocytopenia can [also] be dose limiting. Unfortunately, there are not many good agents that you can combine because most chemotherapy drugs will cause thrombocytopenia. Those are [aspects to consider] in the future. For us, thrombocytopenia can be permissive because usually we can accept a platelet count as low as 20,000 if there’s no bleeding and patients [do not require] anticoagulation.

Regarding BTK inhibitors in relapsed/refractory chronic lymphocytic leukemia, how is resistance being addressed for this patient population?

Pirtobrutinib [Jaypirca] is a noncovalent BTK inhibitor designed to get around the most common mutation to covalent BTK inhibitors, [which is] C481S. Additionally, BTK degraders are in development for those that become resistant to noncovalent BTK inhibitors.

What were some important follicular lymphoma–related updates from the 2025 ASCO Annual Meeting and 2025 EHA Congress?

[Five notable abstracts were presented]. The first abstract, [published in Blood Cancer, and presented at the 2025 EHA Congress] was a retrospective cohort study looking at the clinical characteristics and outcomes of patients with incidental follicular lymphoma. The study found that patients with incidental follicular lymphoma have more favorable prognostic features at the time of diagnosis, but similar overall survival and event-free survival compared with patients with symptomatic follicular lymphoma at presentation.

The second abstract, published in Hematological Oncology and presented at the 2025 International Conference on Malignant Lymphoma, was the primary analysis of the phase 3 PERSPECTIVE study [NCT02947347] of ibrutinib [Imbruvica] plus rituximab [Rituxan] vs placebo plus rituximab in patients with previously untreated follicular lymphoma who were not [eligible] for chemoimmunotherapy. The study showed improved progression-free survival [PFS], which was the primary outcome in the experimental arm; however, the applicability of this regimen remains to be determined in this population.

The third abstract was an interim analysis of the phase 2 MorningSun study [NCT05207670] of subcutaneous mosunetuzumab-axgb [Lunsumio] in patients with previously untreated high tumor burden follicular lymphoma. The study showed a high overall and complete metabolic response rate with manageable toxicity, compatible with outpatient administration in the community setting.

The fourth abstract reviewed the final results of the phase 3 inMIND study [NCT04680052] of tafasitamab-cxix [Monjuvi] vs placebo plus lenalidomide [Revlimid] and rituximab in patients with relapsed/refractory follicular lymphoma [or marginal zone lymphoma (MZL)]. The study met its primary [end point] of improving PFS and has led to the FDA approval of this combination in patients with follicular lymphoma.

The fifth abstract reviewed the preliminary safety and efficacy data of the [phase 1/2] SIDNEY study [NCT04669171] utilizing a novel off-the-shelf peptide immunotherapy EO2463 in combination with lenalidomide and rituximab in patients with relapsed/refractory follicular lymphoma and MZL. This preliminary analysis showed that the peptide immunotherapy was safe and led to a quick, robust, and durable immune response with complete response rates numerically higher than those expected for the combination of lenalidomide and rituximab alone.

How has the role of pola-R-CHP helped address an unmet need in patients with untreated diffuse LBCL?

Historically, 40% patient with patients with LBCL experience disease progression following standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] therapy. The [phase 3] POLARIX trial [NCT03274492] demonstrated that polatuzumab vedotin-piiq [Polivy] plus rituximab, cyclophosphamide, doxorubicin, and prednisone [Pola-R-CHP] addresses this unmet need by significantly improving PFS in this high-risk population, while maintaining a comparable safety profile and reducing the need for subsequent therapies. Moreover, the observed benefit in the activated B-cell like subtype highlights a step toward more precision-based treatment approaches in the future.

Without head-to-head studies to compare axi-cel with liso-cel, what is the decision-making process like in clinical practice for the treatment of patients with LBCL?

Both axi-cel and liso-cel have demonstrated high efficacy and tolerable toxicity profiles in patients with refractory LBCL or early relapse. In the absence of head-to-head trials, product selection is often individualized, taking into consideration center experience and patient-specific factors such as age and comorbidities. We may lean toward liso-cel in more medically complex or older patients, given its favorable safety profile, and axi-cel may be considered for patients who are younger and fit to tolerate more intensive therapy. However, real-world studies are important to guide evidence-based clinical decision-making.