Dr Battiwalla on the Utility of Emerging Therapies for Aggressive FL Management

“We have a fair number of ways to target CD19 through CAR T-cell therapies as well as bispecific antibodies, EZH2, and [now] BTK inhibitors.”

Minoo Battiwalla, MD, MS, director, Blood Cancer Outcomes Research, Sarah Cannon Research Institute, TriStar Medical Group, discusses how emerging therapies, such as bispecific T-cell engagers (BiTEs), EZH2 inhibitors, and BTK inhibitor combinations, contribute to the treatment of patients with aggressive variants of follicular lymphoma (FL).

Emerging therapies are transforming the management of aggressive variants of FL, a condition traditionally considered indolent but with certain subtypes that demonstrate rapid progression, often defined as progression of disease within 24 months, Battiwalla begins. These aggressive cases demand more intensive therapeutic approaches and often involve multiple lines of treatment, he says.

Historically, anti-CD19 CAR T-cell therapies, such as axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah), have been established as options for refractory cases, Battiwalla expands. However, new agents and combinations are broadening the therapeutic armamentarium, according to Battiwalla. BiTEs, like mosunetuzumab-axgb (Lunsumio), provide a novel mechanism for targeting CD20-positive B cells, he explains. The EZH2 inhibitor tazemetostat (Tazverik) has shown efficacy in both 

-mutated and wild-type FL and demonstrates enhanced activity when combined with lenalidomide (Revlimid) plus rituximab (Rituxan). These combinations show promise in increasing potency and simultaneously maintaining manageable toxicity, Battiwalla adds.

BTK inhibitors, such as zanubrutinib (Brukinsa), are emerging as another cornerstone in FL management, Battiwalla expands. Their potential synergy with anti-CD20 agents offers an appealing therapeutic avenue with nonoverlapping toxicities, which may improve patient outcomes and tolerability, he emphasizes, stating that these therapies expand the toolkit for addressing aggressive FL and may minimize the burden of adverse effects.

Ultimately, the goal in treating patients with advanced FL is to prolong survival, as a cure is unlikely in these disease stages, Battiwalla reports. Selecting effective combinations of emerging therapies and mitigating toxicity is critical to achieving the best outcomes for patients with aggressive FL subtypes, Battiwalla concludes.

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Minoo Battiwalla, MD, MS, discusses how emerging therapies contribute to the management of aggressive variants of follicular lymphoma.

Dr Battiwalla on Limitations to CAR T-Cell Therapy Access in Hematologic Malignancies

Minoo Battiwalla, MD, MS, director, Blood Cancer Outcomes Research, Sarah Cannon Research Institute, TriStar Medical Group, discusses both the benefits and the limitations of treatment with CAR T-cell therapy in patients with non-Hodgkinlymphoma (NHL) and multiple myeloma. He also highlights the safety profiles and financial toxicities that are associated with with this effective treatment option.

CAR T-cell therapy has demonstrated significant effectiveness in various indications, such as NHL and multiple myeloma, Battiwalla states. However, the primary challenge surrounding CAR T-cell therapy lies in managing patient access, he emphasizes, noting that this access is often restricted for several reasons.

First, the substantial cost associated with this treatment necessitates a comprehensive evaluation prior to administration, he begins. This financial burden can limit patient access to therapy, according to Battiwalla, who adds that the risk of severe toxicity is another critical factor. As the administration of CAR T-cell therapies expands beyond specialized transplant centers, hematologists are concerned about treating patients who may experience unexpectedly high levels of toxicity, Battiwalla reports. These toxicities, including high-grade cytokine release syndrome and neurotoxicity, require immediate intervention and can be particularly alarming for non-specialized health care facilities, he says. Currently, no commercially available CAR T-cell therapies are adequately prepared for broader community application, Battiwalla continues.

Furthermore, there is often a prolonged wait time between when patients are initially referred for treatment and when they receive therapy, he reports. Although this duration has decreased due to more efficient intake processes, it remains a significant barrier, especially for patients with aggressive variants of large cell lymphoma who cannot afford to delay treatment, he continues. In this context, the careful selection of bridging and continuation therapies to expedite patient access to CAR T-cell therapy is essential, Battiwalla emphasizes. This process demands substantial effort and coordination between referring community oncologists and treating transplantcenters, he says. The access barriers for these highly effective therapies present a considerable challenge within the field, Battiwalla concludes.

Minoo Battiwalla, MD, MS, discusses both the benefits and the limitations of treatment with CAR T-cell therapy across hematologic malignancies.

Dr Battiwalla on the Potential Roles of FLT3-ITD and Menin Inhibitors in AML Management

Minoo Battiwalla, MD, MS, director, Blood Cancer Outcomes Research, Sarah Cannon Research Institute, TriStar Medical Group, discusses the integration of FLT3-ITD inhibitors into the frontline management setting for acute myeloid leukemia (AML) and how this shift has changed the trajectory of targeted therapy for this disease. He also highlights data with the use of menin inhibitors in AML.

The integration of FLT3-ITD inhibitors into frontline management of AML has significantly shifted the paradigm of targeted therapies for this disease, Battiwalla begins. Historically, patients with AML were treated with either aggressive induction chemotherapy or venetoclax (Venclexta)–based regimens for patients needing less intensive management, he explains. However, as the understanding of AML’s molecular mutations has advanced, the ability to target specific mutations has greatly improved outcomes, Battiwalla emphasizes.

The introduction of FLT3-ITD inhibitors marked a breakthrough as the first successful targeted therapy in AML, he continues. These inhibitors are now an integral part of both frontline and maintenance treatment, according to Battiwalla. Their success has set a foundation for the development of additional targeted therapies, including inhibitors aimed at mutations in the 

 genes, further expanding treatment options for patients, Battiwalla explains.

The emergence of menin inhibitors represents another promising advancement in AML therapy, he expands. These agents are relevant for patients with 

 mutations or 11q23 gene rearrangements that result in 

translocations. Early clinical trials investigating menin inhibitors, including those evaluating oral formulations of these agents, have demonstrated encouraging results, including high overall response rates, in several subsets of AML, Battiwalla adds. These promising outcomes indicate that menin inhibitors may soon become a key component of the AML treatment paradigm, he says.

Although no menin inhibitors have received FDA approval, several are nearing regulatory authorization, and it is anticipated that menin inhibitors will be incorporated into various lines of therapy, Battiwalla emphasizes. Theapproval of these agents would represent a significant shift in the AML treatment paradigm, offering new hope for patients with specific genetic mutations, Battiwalla concludes.

Minoo Battiwalla, MD, MS, discusses the potential of FLT3-ITD and menin inhibitors to broaden the acute myeloid leukemia treatment paradigm.

Dr Battiwalla on the Expanding Use of Bispecific Antibodies in NHL

Minoo Battiwalla, MD, MS, director, Blood Cancer Outcomes Research, Sarah Cannon Research Institute, TriStar Medical Group, 

discusses the variety of bispecific antibodies

 available or under investigation for patients with non-Hodgkin lymphoma (NHL), including those with diffuse large B-cell lymphoma (DLBCL).

Bispecific antibodies have emerged as a promising treatment option for patients with NHL, offering an effective and timelieralternative to CAR T-cell therapy, Battiwalla begins. Although CAR T-cell therapies are highly potent, they are also associated with an increased risk of toxicity, he notes. Bispecific antibodies may serve as a viable treatment option for patients with lower performance status, as well as those who have previously undergone stem cell transplantation or CAR T-cell therapy, he says.

The number of bispecific antibodies under investigation in NHL is rapidly expanding, with several agents already FDA approved for various indications, Battiwalla notes. 

Mosunetuzumab-axgb (Lunsumio) is approved

 for patients with follicular lymphoma (FL) who have progressed on 2 or more prior lines of therapy. 

 are both approved for patients with DLBCL who have relapsed following 2 or more lines of therapy. Notably, the biologics license application for odronextamab (REGN1979) for the treatment of patients with relapsed/refractory DLBCL and FL who have received at least 2 prior lines of therapy 

Despite the variety of treatment options for patients with NHL, most cancer centers may initially choose agents based on familiarity rather than specific clinical data, as differences between these agents are often subtle, Battiwalla describes. Epcoritamab stands out in the treatment paradigm because of its subcutaneous administration, which may be more convenient for patients than intravenous agents, he explains. Since all these agents have maintenance dosing schedules that range from every 2 weeks to every 4 weeks, there is minimal differentiation regarding dosing frequency, he emphasizes. Overall, the continued integration of bispecific antibodies into the therapeutic arsenal for aggressive NHL subtypes will require careful consideration of available data and dosing information, Battiwalla concludes.

Minoo Battiwalla, MD, MS, discusses the variety of bispecific antibodies evaluated for patients with NHL, including DLBCL.

Minoo Battiwalla, MD, discusses remaining unmet needs for patients with multiple myeloma and potential strategies being explored to address these needs.

Dr Battiwalla on Addressing Unmet Needs in Multiple Myeloma  

Minoo Battiwalla, MD, director, Blood Cancer Outcomes Research, Sarah Cannon Research Institute, discusses remaining unmet needs for patients with multiple myeloma and potential strategies being explored to address these needs.

Myeloma remains a challenging disease with severe manifestations, Battiwalla begins. Although significant progress has been made in the management of standard-risk disease, addressing the needs of high-risk patients remains a critical challenge, he says. In the transplant-eligible population, the use of quadruplet therapy has been effective at mitigating the impact of single cytogenetic high-risk abnormalities on patient outcomes, Battiwalla states. However, the efficacy of this approach for patients with double cytogenetic high-risk abnormalities is still unclear, indicating a need for more effective therapies in this subset of patients, he explains.

For transplant-ineligible patients, the combination of the anti-CD38 monoclonal antibody daratumumab (Darzalex) with lenalidomide (Revlimid) and dexamethasone has proven to be highly effective, Battiwalla continues. Nonetheless, these patients could also benefit from advances made in the transplant-eligible arena, he says. One such advance is the earlier involvement of CAR T-cell therapy, according to Battiwalla. Ciltacabtagene autoleucel (Carvykti; cilta-cel) has demonstrated reduced toxicity when used in the second-line setting compared with its use in the fifth-line setting, making earlier treatment with CAR T-cell therapy a viable option for transplant-ineligible patients, Battiwalla reports. This shift in treatment strategy could potentially improve outcomes for this patient population, he emphasizes.

Another significant unmet need is the incorporation of bispecific antibodies into earlier lines of therapy, Battiwalla says. Bispecific antibodies have shown considerable promise in treating patients with myeloma, but their optimal placement in the treatment paradigm is still being determined, he explains. Finding a home for bispecific antibodies in the earlier-line setting could enhance treatment efficacy and provide new avenues for managing the disease more effectively, Battiwalla emphasizes.

Overall, the focus of research in myeloma must now shift towards developing and integrating more effective therapies for high-risk patients, Battiwalla concludes. This includes optimizing the use of existing therapies, such as quadruplet regimens and CAR T-cell therapy, as well as identifying the best way to incorporate emerging treatments, such as bispecific antibodies.

Dr Battiwalla on Addressing Unmet Needs in Multiple Myeloma

Minoo Battiwalla, MD, discusses recent advancements in the multiple myeloma treatment paradigm.

Dr Battiwalla on Advancements in the Multiple Myeloma Treatment Paradigm

Minoo Battiwalla, MD, director, Blood Cancer Outcomes Research, Sarah Cannon Research Institute, discusses recent advancements in the multiple myeloma treatment paradigm.

Changes in the approach to multiple myeloma management over the past year are characterized by key advancements in induction therapy and a significant expansion of FDA indications for CAR T-cell therapies in this disease, Dr. Battiwalla begins.

One notable shift is the widespread adoption of quadruplet induction therapy for transplant-eligible multiple myeloma patients, Dr. Battiwalla states. Upfront use of this approach, as suggested by findings from the phase 2 GRIFFIN trial (NCT02874742) and subsequently confirmed by the phase 3 PERSEUS trial (NCT03710603), has been established as the standard of care for patients with transplant-eligible multiple myeloma, regardless of cytogenetic risk status, Dr. Battiwalla details. Additionally, there is now a recognized emphasis on using consolidation therapy post-transplant, which typically involves 2 cycles of the quadruplet regimen, he adds.

Another key development is the incorporation of CAR T-cell therapies, which were previously confined to the fifth-line setting, into earlier lines of treatment, Dr. Battiwalla continues. 

Idecabtagene vicleucel (ide-cel; Abecma) received FDA approval

 in April 2024 for the treatment of adult patients with relapsed/refractory multiple myeloma following 2 or more prior lines of therapy, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody. In the same month, 

ciltacabtagene autoleucel (cilta-cel; Carvykti) was approved

 by the FDA for patients previously exposed to 1 or more prior lines of therapy, including an IMiD or PI, and who are refractory to lenalidomide (Revlimid). Both regimens significantly improved median progression-free survival vs standard regimens, Battiwalla reports. Notably, the toxicity profiles of CAR T-cell therapies appear more manageable when used in earlier lines of therapy, likely due to lower disease burden compared to later-line settings, he says.

Overall, these advancements represent a shift in the treatment paradigm for multiple myeloma, offering more effective and innovative options for patients at various stages of the disease, Dr. Battiwalla concludes.

Dr Battiwalla on Outpatient CAR T-Cell Therapy Administration in Hematologic Malignancies

Minoo Battiwalla, MD, director, Blood Cancer Outcomes Research, Sarah Cannon Research Institute, discusses preliminary findings from a study evaluating the standardization of outpatient care after CAR T-cell therapy in patients with hematologic malignancies.

Investigators performed a study among sites in the Transplant and Cellular Therapy Network evaluating patient adherence, time spent on monitoring, and clinical outcomes with outpatient care after CAR T-cell therapy administration. Outpatient care was delivered using an FDA-cleared virtual care platform, a wearable device transmitting vital signals, a tablet, an axillary temperature patch, and a blood pressure cuff. Patients also engaged daily with decentralized virtual nurses throughout the duration of the study. Additionally, patients were required to visit the clinic in person during the highest-risk period of CAR T-cell administration, which was days 1 through 14.

In total, 40 patients with non-Hodgkin lymphoma (60%), plasma cell disorder (29%), or acute lymphoblastic leukemia (11%) received CAR T-cell therapy and completed the outpatient CAR T-cell therapy protocol.

This study found the multicentric, standardized approach to care after CAR T-cell therapy administration to be feasible, Battiwalla says. Moreover, in this study, remote patient monitoring was feasible and led to a reduction in the number of days patients spent in the hospital, Battiwalla emphasizes. Patients who received planned inpatient CAR T-cell therapy and subsequent inpatient care required a median of 16 days of hospitalization. Of the patients who received outpatient care after CAR T-cell therapy, 83% required hospitalization, and 28% required admission to the intensive care unit. Among the patients who required hospital observation and/or hospital admission, the median number of days to discharge from the hospital was 4, indicating that outpatient administration decreases hospital resource use, Battiwalla says.

Furthermore, safety was not compromised when patients received outpatient CAR T-cell therapy, Battiwalla explains. A total of 30 patients had no cytokine release syndrome, although 15 of those patients required hospitalization for other reasons.

Minoo Battiwalla, MD, discusses findings from a study of outpatient care after CAR T-cell therapy in patients with hematologic malignancies.

Minoo Battiwalla, MD

Articles

Dr Battiwalla on the Utility of Emerging Therapies for Aggressive FL Management

Dr Battiwalla on Limitations to CAR T-Cell Therapy Access in Hematologic Malignancies

Dr Battiwalla on the Potential Roles of FLT3-ITD and Menin Inhibitors in AML Management

Dr Battiwalla on the Expanding Use of Bispecific Antibodies in NHL

Dr Battiwalla on Addressing Unmet Needs in Multiple Myeloma

Dr Battiwalla on Advancements in the Multiple Myeloma Treatment Paradigm

Dr Battiwalla on Outpatient CAR T-Cell Therapy Administration in Hematologic Malignancies