Larry Anderson, MD, PhD, associate professor in the Department of Internal Medicine of the Division of Hematology/Oncology, at Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses the methods utilized in the phase 2 KarMMa trial (NCT03361748) in multiple myeloma.

The KarMMa trial, which had updated data presented during the 2021 

, investigated the efficacy and safety of idecabtagene vicleucel (ide-cel; Abecma) in patients with relapsed/refractory multiple myeloma.

Prior to ide-cel administration, peripheral blood autologous T cells are taken via leukapheresis from a patient and modified with a viral vector to express a CAR T-cell receptor that recognizes BCMA, a plasma cell–specific surface protein on myeloma cells that is not expressed on other normal tissue, Anderson explains. In the KarMMa trial, 128 patients with relapsed/refractory multiple myeloma who received at least 3 prior lines of therapy were treated with ide-cel across a target dose range of 150 x 106 to 450 x 106 CAR T cells, Anderson adds. Patients had received a median of 6 prior lines of therapy, with a range from 3 to 16, Anderson concludes.

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Larry Anderson, MD, PhD, discusses the methods utilized in the phase 2 KarMMa trial in multiple myeloma. 

Dr. Anderson on the Methods Utilized in the KarMMa Trial in Multiple Myeloma 

Larry Anderson, MD, PhD, associate professor, Department of Internal Medicine, Division of Hematology/Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the challenges faced with CAR T-cell therapy in patients with multiple myeloma.

Although CAR T-cell therapy has demonstrated efficacy as a therapeutic option for this patient population, this modality is known to come with specific associated toxicities, according to Anderson. As such, the availability of CAR T-cell therapy is currently limited to large referral centers, such as bone marrow transplant centers or academic medical centers that have expertise in stem cell and cell therapies, Anderson explains.

Additionally, CAR T-cell therapy often requires a multidisciplinary team comprised of social workers, caregivers, and others, Anderson says. After receiving CAR T-cell therapy, patients cannot drive for 2 months due to the risk of neurotoxicity and seizures; as such, patients receiving this modality may require a caregiver. Moreover, due to fevers or other symptoms of cytokine release syndrome, other medical professionals a patient visits will need to be made aware of the treatment, Anderson adds. Additionally, patients generally need to live within hours of their treatment center for at least the first month of therapy, which could impact their lifestyle, according to Anderson.

However, the challenges faced with CAR T-cell therapy are often balanced out by the freedom of not needing to be on additional treatment for the coming years, Anderson concludes.

Larry Anderson, MD, PhD, discusses the challenges faced with CAR T-cell therapy in patients with multiple myeloma.

Dr. Anderson on the Challenges Faced With CAR T-Cell Therapy in Myeloma

Larry Anderson, MD, PhD, associate professor in the Department of Internal Medicine of the Division of Hematology/Oncology, at Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses outcomes with idecabtagene vicleucel (ide-cel, Abecma) in patients with relapsed/refractory multiple myeloma, as demonstrated in the phase 2 KarMMa trial (NCT03361748).

The updated results from the study, presented at the 2021 

, showed that ide-cel yielded a median overall survival (OS) of 24.8 months in heavily pretreated patients with triple-class exposed relapsed/refractory multiple myeloma, according to Anderson. Overall survival was similar for those who had received 3 or more prior lines of therapy, Anderson explains. Additionally, the median OS was more than 20 months for patients with extramedullary and triple-class refractory disease.

The CAR T-cell therapy elicited an overall response rate (ORR) of 73% and resulted in a median progression-free survival (PFS) of 8.6 months, Anderson explains. Notably, in the subset of patients who received the highest dose of CAR T cells, the ORR was even higher, at 81%, with a complete response (CR)rate of 39%. In this subset, the median PFS was 12.2 months, Anderson says. 

Notably, responses to ide-cel were durable, with a median duration of response of 10.9 months among all treated patients. The durability increased with depth of response, to 21.5 months of remission for those who achieved a CR and 41% of these patients were still in remission 2 years later, Anderson concludes. 

Larry Anderson, MD, PhD, discusses outcomes with idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma, as demonstrated in the phase 2 KarMMa trial.

Dr. Anderson on Updated KarMMa Data With Ide-Cel in Multiple Myeloma 

Larry Anderson, MD, PhD, associate professor in the Department of Internal Medicine of the Division of Hematology/Oncology, at Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses recent advances made with novel therapies in multiple myeloma.

The frontline treatment setting for multiple myeloma is where most of the changes are happening, says Anderson. The field has seen some new approvals, such as the monoclonal antibody daratumumab (Darzalex). The drug is now being incorporated into frontline therapy, at least in patients who are ineligible for transplant, says Anderson. Other research has evaluated the incorporation of daratumumab into multidrug regimens in the pre-transplant setting, as well; these efforts look very promising, according to Anderson. Similar combinations with daratumumab and carfilzomib (Kyprolis) in the relapsed/refractory setting have been shown to result in deep remissions.

Data with bispecific T-cell engagers (BiTEs) have also been reported. At the 2019 ASH Annual Meeting, a presentation on CC-093269 showed an 89% response rate with this approach in patients with heavily refractory multiple myeloma who were treated with >6 mg; these patients experienced very deep responses. This approach offers a way to provide patients with T-cell immunity without having to generate CAR T-cells, Anderson adds.

CAR T-cells are also very exciting but the challenge with this approach is that it takes approximately 1 month to genetically engineer and grow the cells, says Anderson. Sometimes patients cannot that long for the T-cells because their disease is progressing.

Larry Anderson, MD, PhD, discusses recent advances made with novel therapies in multiple myeloma.

Dr. Anderson on Recent Advances With Novel Therapies in Multiple Myeloma

Larry Anderson, MD, PhD, associate professor in the Department of Internal Medicine of the Division of Hematology/Oncology, at Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses recent advances made with novel therapies in multiple myeloma.

The frontline treatment setting for multiple myeloma is where most of the changes are happening, says Anderson. The field has seen some new approvals, such as the monoclonal antibody daratumumab (Darzalex). The drug is now being incorporated into frontline therapy, at least in patients who are ineligible for transplant, says Anderson. Other research has evaluated the incorporation of daratumumab into multidrug regimens in the pre-transplant setting, as well; these efforts look very promising, according to Anderson. Similar combinations with daratumumab and carfilzomib (Kyprolis) in the relapsed/refractory setting have been shown to result in deep remissions.

Data with bispecific T-cell engagers (BiTEs) have also been reported. At the 2019 ASH Annual Meeting, a presentation on CC-093269 showed an 89% response rate with this approach in patients with heavily refractory multiple myeloma who were treated with >6 mg; these patients experienced very deep responses. This approach offers a way to provide patients with T-cell immunity without having to generate CAR T-cells, Anderson adds.

Larry Anderson, MD, PhD, associate professor, Department of Internal Medicine, Division of Hematology/Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the phase II GRIFFIN trial examining the addition of daratumumab (Darzalex) to lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (D-RVd) in patients with multiple myeloma.

One of the key studies that was presented at 2019 ASH Annual Meeting is the GRIFFIN study, says Anderson. That randomized trial evaluated the use of up-front daratumumab with RVd. The stringent complete response (sCR) rate after a median follow-up of 22.1 months was 62.6% with D-RVd versus 45.4% with RVd (odds ratio, 1.98; 95% CI, 1.12-3.49; 

 = .0177). The overall CR rate was also improved with D-RVd, at 79.8% versus 60.8% (

 = .0045), and the proportion of patients achieving minimal residual disease negativity was twice as high with D-RVd. At 24 months, both regimens had led to progression-free survival rates exceeding 85% and overall survival rates exceeding 90%. In that study physicians are seeing significantly more deep remissions and molecular remissions, or minimal residual disease negativity, concludes Anderson.

Larry Anderson, MD, PhD, discusses the phase II GRIFFIN trial examining the addition of daratumumab (Darzalex) to lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (D-RVd) in patients with multiple myeloma.

Dr. Anderson on the GRIFFIN Study With D-RVd in Multiple Myeloma

Larry Anderson, MD, PhD, associate professor, Department of Internal Medicine, Division of Hematology/Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses recent FDA approvals in multiple myeloma.

In June 2019, the FDA approved the combination of daratumumab (Darzalex), lenalidomide (Revlimid) and dexamethasone (DRd) for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation.

The approval was based on results of the phase III MAIA trial which demonstrated a 44% reduction in the risk of disease progression or death with DRd compared with lenalidomide/dexamethasone (Rd) alone. Additionally, the median progression-free survival was not reached versus 31.9 months in the DRd and Rd arms, respectively.

In July 2019, selinexor (Xpovio), a first-in-class Selective Inhibitor of Nuclear Export, was granted accelerated approval by the FDA in combination with dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma whose disease is refractory to ≥2 proteasome inhibitors, ≥2 immunomodulatory agents, and a CD38-targeted monoclonal antibody.

The approval was based on findings from Part 2 of the phase II STORM trial which showed an overall response rate of 25.3% with the combination (95% CI, 16.4-36.0). Patients on selinexor may experience nausea. Preemptive management with an aggressive antiemetic can help improve the tolerability of the regimen, concludes Anderson.

Larry Anderson, MD, PhD, discusses recent FDA approvals in multiple myeloma.

Larry Anderson, MD, PhD

Articles

Dr. Anderson on the Methods Utilized in the KarMMa Trial in Multiple Myeloma

Dr. Anderson on the Challenges Faced With CAR T-Cell Therapy in Myeloma

Dr. Anderson on Updated KarMMa Data With Ide-Cel in Multiple Myeloma

Dr. Anderson on Recent Advances With Novel Therapies in Multiple Myeloma

Dr. Anderson on Recent Advances With Novel Therapies in Multiple Myeloma

Dr. Anderson on the GRIFFIN Study With D-RVd in Multiple Myeloma

Dr. Anderson on Recent FDA Approvals in Multiple Myeloma