Natalie S. Callander, MD, associate professor, Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, director, University of Wisconsin Carbone Cancer Center Myeloma Clinical Program, discusses ongoing and planned clinical trials evaluating the use of novel therapeutic regimens in multiple myeloma.

The single-arm, multicenter, phase 2 BMTCTN1902 trial (NCT05032820) is investigating the use of anti-BCMA CAR T-cell therapy (bb2121) for patients with multiple myeloma whose disease has had a suboptimal response to autologous stem cell transplantation (ASCT) followed by 1 year of maintenance lenalidomide (Revlimid), Callander begins. It is hypothesized that CAR T-cell therapy will upgrade patient responses, Callander states. Responses are deemed suboptimal if they are less than a complete response (CR) after 3 months of maintenance therapy, she notes. The study's primary outcome is the efficacy of BCMA CAR-T cell therapy, which is defined as the patient having a response of CR or better by the 6-month time point following treatment. 

Additionally, the registrational phase 2 iMMagine-1 trial (NCT05396885) is investigating the use of a novel CAR T-cell asset, CART-ddBCMA for patients with relapsed/refractory multiple myeloma in later lines, Callander says. Unlike standard CAR T-cell therapies, this agent is designed with a novel synthetic, animal variant region rather than a single-chain variant region. This different binding domain may make the combination less immunogenic, Callander explains. The trial has begun enrollment.

Future avenues for research at Carbone Cancer Center include the planned investigation of a triplet combination comprised of carfilzomib (Kyprolis), isatuximab-irfc (Sarclisa), selinexor (Xpovio), and dexamethasone, Callander continues.

Data from the phase 2 MASTER-2 trial (NCT03224507) showed the viability of quadruplet consolidation regimens with carfilzomib in this population. The minimal residual disease (MRD)–guided trial evaluated a combination of daratumumab (Darzalex), lenalidomide, carfilzomib and dexamethasone (KRd) in patients with newly diagnosed multiple myeloma who had undergone autologous hematopoietic cell transplantation, Callander reports. There is also interest in investigating the use of an iberdomide-containing consolidation maintenance therapy to improve response rates after ASCT, Callander concludes.

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Natalie S. Callander, MD, discusses several ongoing and planned  clinical trials evaluating the use of novel therapeutic regimens in multiple myeloma.

Dr Callander on Ongoing and Future Clinical Trials in Multiple Myeloma at Carbone Cancer Center

Natalie S. Callander, MD, associate professor, Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health; director, University of Wisconsin Carbone Cancer Center Myeloma Clinical Program, discusses the significance of the phase 3 ATLAS (NCT02659293), phase 2 FORTE (NCT02203643), and phase 2 MASTER (NCT03224507) trials in patients with multiple myeloma.

The University of Wisconsin School of Medicine and Public Health participated in the minimal residual disease (MRD)–guided MASTER trial, which evaluated the quadruplet consolidation regimen comprised of daratumumab (Darzalex), lenalidomide (Revlimid), carfilzomib (Kyprolis), and dexamethasone (KRd) in patients with newly diagnosed multiple myeloma who had undergone autologous hematopoietic cell transplantation, Callander says. At a median follow-up of 25.1 months, 80% of patients had achieved MRD negativity. The 2-year progression-free survival (PFS) rate was 87%.

Additionally, findings from the FORTE trial support the use of carfilzomib plus lenalidomide as maintenance therapy in this population, Callander explains. In the maintenance setting, FORTE randomized patients with newly diagnosed multiple myeloma to receive either carfilzomib plus lenalidomide or lenalidomide alone after induction and consolidation therapies. At a median follow-up of 37.3 months from maintenance randomization, the 3-year PFS rate was 75% in patients who received carfilzomib plus lenalidomide vs 65% in those who received lenalidomide alone.

Another trial, ATLAS, is investigating KRd vs lenalidomide alone as maintenance therapy in patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplant. Findings from the interim analysis from this trial showed that, at a median follow-up of 33.8 months, patients who received KRd achieved a median PFS of 59.1 months vs 41.4 months for those who received lenalidomide alone.

Although more research is necessary to determine the most effective maintenance strategy for patients with newly diagnosed multiple myeloma, the data from ATLAS support the use of triplet combinations in the maintenance setting, which may be particularly beneficial for high-risk patients, Callander concludes.

Natalie S. Callander, MD, discusses the significance of the phase 3 ATLAS, phase 2 FORTE, and phase 2 MASTER trials in patients with multiple myeloma.

Dr Callander on Investigational Maintenance Regimens in Multiple Myeloma

Natalie S. Callander, MD, associate professor, Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health; director, University of Wisconsin Carbone Cancer Center Myeloma Clinical Program, discusses the potential benefits of referring patients with multiple myeloma to CAR T-cell therapy earlier in their disease course.

The 2 CAR T-cell therapies currently approved for patients with multiple myeloma are idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti). Ide-cel was approved for patients with multiple myeloma in 2021 based on findings from the phase 2 KarMMa trial (NCT03361748), in which ide-cel infusion led to an overall response rate (ORR) of 72%. Cilta-cel was approved for patients with relapsed/refractory multiple myeloma in February 2022 based on data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207), in which patients who received this therapy achieved an ORR of 97%.

However, based on findings from the phase 3 CARTITUDE-4 (NCT04181827) and KarMMa-3 (NCT03651128) trials, the FDA may revise the labeling for cilta-cel and ide-cel in multiple myeloma, Callander says. Currently, both CAR T-cell products are approved for patients who have already received at least 4 prior lines of therapy, although heavily pretreated patients are often no longer fit for CAR T-cell therapy, or do not derive the most benefit from this treatment, Callander explains.

The CARTITUDE-4 trial met its primary end point of progression-free survival (PFS) improvement with cilta-cel vs pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd) in patients with multiple myeloma who were relapsed/refractory to 1 to 3 prior lines of therapy. Additionally, in the KarMMa-3 trial, patients with multiple myeloma who were relapsed/refractory to 2 to 4 prior lines of therapy had a median PFS of 13.3 months with ide-cel vs 4.4 months with standard of care.

Data from CARTITUDE-4 and KarMMA-3 support the early referral of patients to CAR T-cell therapy so they are fit to receive this treatment and have the potential for a long period off therapy before requiring further treatment, Callander emphasizes. The combination of early discussions about CAR T-cell therapy with patients and potential changes to the FDA labeling for these products may positively alter the multiple myeloma treatment landscape, Callander concludes.

Natalie S. Callander, MD, discusses the potential benefits of referring patients with multiple myeloma to CAR T-cell therapy earlier in their disease course.

Dr Callander on Early CAR T-cell Therapy Referrals in Multiple Myeloma

Jason Porter, MD, Janakiraman Subramanian, MD, Natalie S. Calendar, MD, Parameswaran Hari, MD, MRCP, and Kevin Kalinsky, MD, MS, discuss the importance of the Institutional Perspectives in Cancer (IPC) webinars.

The IPC webinars allow oncologists to review and present large sets of data to their peers who may not be able to attend meetings or who have a specific focus in a particular tumor type, Porter, a oncologist/hematologist, and director, Lung Cancer disease research group, West Cancer Center and Research Institute, says. These programs allow attendees to consume and digest data easily and take what they learned back to their clinical practice, Porter notes. 

According to Subramanian, a medical oncologist and director of Thoracic Oncology, Center for Precision Medicine, at Saint Luke’s Cancer Institute, many colleagues have shared about how useful they found these webinars to be. Additionally, attendees who were not oncologists, such as surgeons or pulmonologists, expressed excitement in how the field of oncology has advanced in recent years, Janakiraman explains.

As so many advances have been made across multiple tumor types, these webinars serve as a way to help consolidate and distill information in a useful way, Callander, a professor of medicine in the Division of Hematology/Oncology at the University of Wisconsin Carbone Cancer Center, adds.

The COVID-19 pandemic has shown that it is possible to utilize technology to deliver short, precise information to a wide audience, Hari, the Armand J. Quick/William F. Stapp Professor of Hematology, and the chief of the Division of Hematology/Oncology, Department of Medicine, at the Medical College of Wisconsin, notes. For those oncologists who typically focus on just 1 tumor type, it is important that those experiences get shared with as many healthcare providers as possible to extend benefits to patients, Hari explains. 

Despite the pandemic, it is important for healthcare providers to be able to come together to discuss data and recent findings, Kalinsky, director of the Glenn Family Breast Center and Breast Medical Oncology at Winship Cancer Institute, and acting associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, concludes.

Jason Porter, MD, Subramanian Janakiraman, MD, Natalie S. Calendar, MD, Parameswaran Hari, MD, MRCP, and Kevin Kalinsky, MD, MS, discuss the importance of the Institutional Perspectives in Cancer webinars. 


Examining the Importance of the Institutional Perspectives in Cancer Webinars

Natalie S. Callander, MD, a professor of medicine in the Division of Hematology/Oncology at the University of Wisconsin Carbone Cancer Center, discusses the potential future of belantamab mafodotin-blmf (Blenrep) in multiple myeloma. 

On August 5, 2020, the FDA granted an accelerated approval to belantamab mafodotin for patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies, including a CD38-directed monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Currently, belantamab mafodotin is the only BCMA-targeted therapy approved in multiple myeloma; therefore, it is being widely adopted into clinical practice, Callander says. However, as more BCMA-targeted options are introduced to the myeloma armamentarium, the role of belantamab mafodotin may change, adds Callander. 

Regarding the agent’s utility, additional data are needed to determine whether belantamab mafodotin could be used as salvage therapy for patients who progress on other BCMA-directed therapies, such as bispecific antibodies or CAR T-cell therapies, Callander explains. Alternatively, these patients may develop a period of refractoriness to BCMA-targeted therapies that would limit the efficacy of belantamab mafodotin. Finally, until the read out of the ongoing DREAMM-9 trial (NCT04091126), the frontline utility of belantamab mafodotin will remain in question, concludes Callander. 

Natalie S. Callander, MD, discusses the potential future of belantamab mafodotin-blmf in multiple myeloma.  



Dr. Callander on the Potential Future of Belantamab Mafodotin in Multiple Myeloma 

Natalie S. Callander, MD, a professor of medicine of the the Division of Hematology/Oncology at the University of Wisconsin Carbone Cancer Center, discusses the expanding role of belantamab mafodotin-blmf (Blenrep) in multiple myeloma.

Belantamab mafodotin, a BCMA-directed antibody-drug conjugate, has demonstrated response rates of just over 30% in patients with heavily pretreated, relapsed/refractory multiple myeloma. Notably, some patients derived deep and durable responses with belantamab mafodotin as monotherapy, explains Callander. 

However, combination regimens with belantamab mafodotin offer potential strategies to improve the response rates observed with single-agent therapy, says Callander. For example, during the 2020 ASH Annual Meeting and Exposition, data from trials evaluating belantamab mafodotin in combinations with bortezomib (Velcade) and pomalidomide (Pomalyst) were presented and showed significantly higher response rates versus those observed with belantamab mafodotin alone.

Additionally, belantamab mafodotin plus bortezomib, lenalidomide (Revlimid), and dexamethasone is being evaluated as an induction regimen for transplant-ineligible patients with newly diagnosed multiple myeloma in the phase 1 DREAMM-9 trial (NCT04091126). Belantamab mafodotin is also being evaluated as a potential option for patients with amyloidosis, concludes Callander.

Natalie S. Callander, MD, discusses the expanding role of belantamab mafodotin-blmf in multiple myeloma.  



Dr. Callander on the Expanding Role of Belantamab Mafodotin in Multiple Myeloma 

Natalie S. Callander, MD, a professor of medicine of the the Division of Hematology/Oncology at the University of Wisconsin Carbone Cancer Center, discusses selecting a frontline treatment strategy for patients with multiple myeloma.

When selecting treatment for patients with newly diagnosed multiple myeloma, it’s important to select an approach that produces deep responses with limited adverse effects, Callander says. If a patient is experiencing organ dysfunction related to their disease, reversing the condition should be a priority, Callander adds. Although a patient may appear to be quite ill, it's important to determine whether symptom bother is because of their disease or due to a preexisting condition, which could make them less fit for treatment.

Although determining transplant eligibility is often done upon diagnosis, this is a factor that can change over time as patients demonstrate clinical improvements, Callander explains. For patients who may undergo an autologous stem cell transplant, it's necessary to select a regimen that will not interfere with stem cell collection, adds Callander.

With many agents emerging in the paradigm, the hope is that some of these options will induce deep responses in patients, Callander says. One of the main areas of debate are the questions of whether a triplet or quadruplet should be used in this patient population and whether a doublet regimen still shows benefit in some patients, Callander concludes.

Natalie S. Callander, MD, discusses selecting a frontline treatment strategy for patients with multiple myeloma.









 Dr. Callander on Selecting a Frontline Treatment Strategy in Multiple Myeloma

Natalie S. Callander, MD, professor of medicine at the Division of Hematology/Oncology, University of Wisconsin Carbone Cancer Center, discusses combinations in multiple myeloma.

Both the POLLUX and CASTOR trials showed high response rates with the use of triplets that involved daratumumab (Darzalex), says Callander.

Callander adds that combinations with elotuzumab (Empliciti), as well as ixazomib (Ninlaro), have shown excellent results as well.

Natalie S. Callander, MD, professor of medicine at the Division of Hematology/Oncology, University of Wisconsin Carbone Cancer Center, discusses combinations in multiple myeloma.
 

Dr. Callander Discusses Combinations in Multiple Myeloma

Natalie S. Callander, MD, professor of medicine at the Division of Hematology/Oncology, University of Wisconsin Carbone Cancer Center, discusses treatment considerations in relapsed and refractory multiple myeloma.

There are 3 principles to keep in mind when treating patients with relapsed or refractory multiple myeloma, says Callander.

The first is to determine where the patient is in their relapse, the second is to evaluate what type of myeloma the patient has, and the final thing is to consider frailty.