Dr Nooka on Integrating Bispecific Antibodies Into the Community Treatment Paradigm for Multiple Myeloma

Ajay K. Nooka, MD, MPH, FACP, hematologist/oncologist, associate professor, Division of Bone Marrow Transplant, associate director, Clinical Research, Winship Cancer Institute of Emory University, discusses the integration of bispecific antibodies into the treatment paradigm for multiple myeloma, particularly within the community oncology setting.

Bispecific antibodies, which have demonstrated impressive response rates in relapsed/refractory patient populations, are becoming increasingly recognized as a viable treatment option, Nooka begins. He emphasizes that bispecific therapies offer response rates of up to 60% in heavily pretreated patients, far surpassing the traditional 30% response rates seen with previous standards of care.

Additionally, progression-free survival (PFS) durations with bispecifics extend beyond 12 months compared with the 3-month PFS often observed in patients who have undergone multiple prior therapies, Nooka expands.

One of the key benefits of bispecific antibodies is their off-the-shelf availability, he says. This allows for the initiation of treatment much more quickly than with CAR T-cell therapy, which requires a more complex cell manufacturing process, Nooka reports. For patients with aggressive disease or limited organ reserve, oncologists are waiting for additional therapies. Where CAR T-cell therapy is not an option, bispecific antibodies provide a critical alternative, he adds

Nooka also highlights the importance of patient-shared decision-making, allowing patients to weigh the options between bispecific antibodies and CAR T-cell therapy based on their individual preferences and clinical needs.

Community oncologists must be prepared to manage the associated toxicities of bispecific therapies, including infections, cytokine release syndrome (CRS), neurotoxicity, and cytopenias, he explains. Having a robust plan in place to monitor and address these potential adverse effects is essential to ensuring the safe integration of bispecific antibodies into clinical practice, Nooka emphasizes

With proper safety measures, bispecific antibodies can serve as an effective and timely therapeutic option for patients with relapsed/refractory multiple myeloma in the community setting, Nooka concludes.

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Ajay K. Nooka, MD, MPH, FACP, discusses the integration of bispecific antibodies into the community treatment paradigm for multiple myeloma.

Dr Nooka on the Utility of Iopofosine I 131 in Waldenström Macroglobulinemia

Ajay K. Nooka, MD, MPH, FACP, professor, director, Myeloma Program, Department of Hematology and Medical Oncology, scientific director, Winship Data and Technology Applications Shared Resource, associate director, Clinical Research, Winship Cancer Institute, Emory University School of Medicine, discusses the rationale for investigating iopofosine I 131 (CLR 131) in the phase 2 CLOVER-WaM trial (NCT02952508) in patients with heavily pretreated, multi-class–refractory Waldenström macroglobulinemia (WM).

Nooka begins by elucidating the significance of iopofosine. This agent constitutes a radioactive iodine and is integral to the concept of phospholipid drug conjugates, he states. Investigators are employing various treatment strategies wherein the drug can be directly targeted to cancer cells, exploiting this mechanism, Nooka says. Certain treatments using this approach involve packing the drug into lipids, enabling specific delivery to cancer cells, which readily take up the drug, he explains. One notable example of a lipid-packed regimen is the combination of daunorubicin/cytarabine (Vyxeos) for patients with acute myeloid leukemia, Nooka reports.

Similarly, within the context of WM, the CLOVER-WaM trial, a pivotal expansion portion of the CLOVER-1 trial, is evaluating iopofosine I 131 as a means of delivering a radioisotope directly to cancer cells, Nooka expands. This is achieved by binding iodine-131 to phospholipid ethers on the cancer cell surface, facilitating uptake by the cancer cell, he relays. As such, this phospholipid drug conjugate can be administered directly to the cancer, minimizing toxicity to surrounding healthy cells, Nooka explains. This mechanism represents a novel and innovative approach to achieving desired tumor responses by specifically targeting cancer cells and simultaneously sparing surrounding tissue from off-target adverse effects, he imparts.

This innovative treatment approach has demonstrated promising results, particularly in B-cell malignancies and specifically in WM, Nooka elucidates. Initial results from the CLOVER-1 trial showed promising response rates in the first few enrolled patients, prompting the expansion of the CLOVER-WaM trial within the WM population, he concludes.

 for patients diagnosed with WM who have undergone at least 2 prior therapies, based on data derived from the CLOVER-1 study.

Ajay K. Nooka, MD, MPH, FACP, discusses the CLOVER-WaM trial of iopofosine I 131 for heavily pretreated, refractory Waldenström macroglobulinemia.

As multiple myeloma (MM) negatively affects patients’ (pts) health-related quality of life (HRQoL), assessment of patient-reported outcomes (PROs) in addition to clinical outcomes is important.

Teclistamab (tec; JNJ-64007957) is an off-the-shelf bispecific antibody that redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing MM cells.

Initial results from the pivotal cohort of the phase 1/2 MajesTEC-1 study demonstrated that tec was well tolerated with encouraging efficacy in pts who received at least 3 prior lines of treatment (LOTs), including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody.

Pts (aged ≥18 years) had documented RRMM (International Myeloma Working Group criteria), progressive/measurable disease, and had previously received ≥3 prior LOT; prior anti-BCMA treatment (tx) was not allowed.

Pts received weekly subcutaneous tec at the recommended phase 2 dose (1.5 mg/kg with step-up doses of 0.06 and 0.3 mg/kg).

PROs were assessed at screening and every even cycle (cycles 2–8 reported here) using the EORTC QLQ-C30 (range: 0–100; higher scores indicate better global health status [GHS] but greater symptom severity [symptom scales]) and the EuroQol 5-dimensional descriptive system (visual analog scale [VAS] range: 0 [worst imaginable health state] to 100 [best imaginable]).

Tx effect was assessed by a mixed-effects model with repeated measures; the proportion of pts with meaningful improvement was defined as a change ≥10 points.

Time to worsening was determined using the Kaplan-Meier estimate.

A total of 110 pts were included (median follow-up: 7.8 mos). Overall PRO compliance rates were high (baseline [BL]: 85–90%; cycles 2–8: 80–94%). Tec improved overall HRQoL as evidenced by improvements in GHS scores (cycles 2–8) and reduction in pain (-4.2 [cycle 2] to -15.1 [cycle 8]), with no overall change in physical functioning and fatigue.

The proportions of pts with meaningful improvements from BL at cycle 8 were GHS: 50%; physical functioning: 35%; pain: 65%; fatigue: 73%; 50% of pts reported meaningful improvement in their overall health (VAS).

Median time to improvement from baseline was ̃1.5 months (with nausea/vomiting and fatigue taking longer to improve), while median time to worsening (all symptoms) ranged from 2 months to not estimable.

Consistent with clinical outcomes, pts treated with tec reported rapid, clinically meaningful improvements in HRQoL. Clinical trial information: NCT04557098.

Martin TG, Moreau P, Usmani SZ et al. Health-related quality of life in patients with relapsed/refractory multiple myeloma (RRMM) treated with teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody: Patient-reported outcomes in MajesTEC-1. Abstract presented at: 2022 American Society of Clinical Oncology, June 3-7, 2022; Chicago, IL & Virtual. Abstract # 8033.

Dr Nooka reviews the patient reported outcomes from the MajesTEC-1 trial in patients with relapsed/refractory multiple myeloma.

Health-related quality of life in patients with relapsed/refractory multiple myeloma (RRMM) treated with teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody: Patient-reported outcomes in MajesTEC-1

Ajay K. Nooka, MD, MPH, FACP, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, medical director, Winship Data and Technology Applications Shared Resource, Winship Cancer Institute, discusses the utility of BCMA as a target in multiple myeloma. 

In oncology, ideal targeted therapies should be directed toward antigens that are specifically expressed on the target cell and not expressed on normal cells, says Nooka. Increased specificity will minimize off-target adverse effects.

BCMA is a specific target that is expressed on myeloma plasma cells and not expressed on normal cells, which is why it has become an effective target for drug development in multiple myeloma, concludes Nooka.

Ajay K. Nooka, MD, MPH, FACP, discusses the utility of BCMA as a target in multiple myeloma.   



Dr. Nooka on the Utility of BCMA as a Target in Multiple Myeloma 

Ajay K. Nooka, MD, MPH, FACP, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, discusses current options for transplant-eligible and -ineligible patients with multiple myeloma.

Three-drug regimens using lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd) are used in transplant-ineligible patients with dose modifications, explains Nooka. For transplant-ineligible patients, the goal is to get the benefit from the triplet with minimal toxicity.

In transplant-eligible patients, transplant is used after a few cycles of induction treatment to gain the depth of response, says Nooka. In transplant-ineligible patients, however, a prolonged induction regimen is used to compensate for the transplant and use continuous treatment to gain similar benefits in transplant-ineligible patients.

RVd or RVd-lite is used for transplant-ineligible patients, but doublets are used in patients who cannot tolerate the other regimens. When using newer induction regimens with RVd and daratumumab (Darzalex), there is no overlapping toxicity with the doublets or triplets in the transplant-ineligible and -eligible settings, concludes Nooka.

Ajay K. Nooka, MD, MPH, FACP, discusses current options for transplant-eligible and -ineligible patients with multiple myeloma.

Ajay K. Nooka, MD, MPH, FACP

Articles

Dr Nooka on Integrating Bispecific Antibodies Into the Community Treatment Paradigm for Multiple Myeloma

Dr Nooka on the Utility of Iopofosine I 131 in Waldenström Macroglobulinemia

Health-related quality of life in patients with relapsed/refractory multiple myeloma (RRMM) treated with teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody: Patient-reported outcomes in MajesTEC-1

Dr. Nooka on the Utility of BCMA as a Target in Multiple Myeloma

Dr. Nooka on Treatment Options for Transplant-Eligible and -Ineligible Multiple Myeloma