UT Soutwestern

Ankit Kansagra, MD, assistant professor in the Department of Internal Medicine at Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses key updates with CAR T-cell therapy in hematologic cancers.

Many fantastic updates have been presented in CAR T-cell therapy in this space, with real-world evidence, says Kansagra. One of these updates has been seen with axicabtagene ciloleucel (axi-cel; Yescarta), which has been out for about 2 years now. More than 500 patients countrywide in more than 50 institutions were treated with this product and were monitored by the Center for International Blood and Marrow Transplant Research. Investigators noticed that this therapy was very efficacious, which is the most important information from the update, adds Kansagra. Sometimes, a drug might appear to be efficacious in clinical trials but that activity is not replicated in the real world. The toxicity or safety profile of the agent in the real-world setting was also very comparable to what had been reported in clinical trials.

Another thing learned in the clinical setting is that medications to prevent or treat cytokine release syndrome (CRS) or other toxicities were more frequently used in the real-world setting than what had been seen in clinical trials. Medications, such as steroids and/or tocilizumab (Actemra), which is a common medication used to treat CRS, were used much more in the real-world setting than in clinical trials, concludes Kansagra.

Videos

Ankit Kansagra, MD, discusses key updates with CAR T-cell therapy in hematologic cancers.

Dr. Kansagra on Updates With CAR T-Cell Therapy in Hematologic Cancers

Prapti Patel, MD, assistant professor in the Department of Internal Medicine at Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the clinical implications of the FDA approval of luspatercept-aamt (Reblozyl) in myelodysplastic syndrome (MDS).

On April 3, 2020, the FDA approved luspatercept for the treatment of anemia failing an erythropoiesis stimulating agent (ESA) and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ring sideroblasts or with MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Prior to the approval, there were no alternative options available for patients who progressed on ESAs other than chemotherapy, explains Patel.

While decitabine and azacitidine are considered “lite” or low-dose chemotherapies, they are associated with significant morbidity and mortality, says Patel.

Though patients with low-risk disease have a 7- to 10-year survival rate, they often have a poor quality of life due to transfusion dependence, explains Patel. As such, luspatercept should be considered for these patients.

Prapti Patel, MD, discusses the clinical implications of the FDA approval of luspatercept-aamt in myelodysplastic syndrome.



Dr. Patel on the Clinical Implications of Luspatercept Approval in MDS

Prapti Patel, MD, assistant professor in the Department of Internal Medicine at Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the clinical implications of the FDA approval of luspatercept-aamt (Reblozyl) in myelodysplastic syndrome (MDS).

On April 3, 2020, the FDA approved luspatercept for the treatment of anemia failing an erythropoiesis stimulating agent (ESA) and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ring sideroblasts or with MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Prior to the approval, there were no alternative options available for patients who progressed on ESAs other than chemotherapy, explains Patel.

While decitabine and azacitidine are considered “lite” or low-dose chemotherapies, they are associated with significant morbidity and mortality, says Patel.

Though patients with low-risk disease have a 7- to 10-year survival rate, they often have a poor quality of life due to transfusion dependence, explains Patel. As such, luspatercept should be considered for these patients.

Prapti Patel, MD, discusses the clinical implications of the FDA approval of luspatercept-aamt in myelodysplastic syndrome.

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.

Farrukh Awan, MD, associate professor in the Department of Internal Medicine, UT Southwestern Medical Center (UTSW), and a member of the Division of Hematology and Oncology at UTSW's Harold C. Simmons Comprehensive Cancer Center and William P. Clements Jr. University Hospital, discusses remaining questions regarding the use of BTK inhibitors and CD20-directed monoclonal antibodies in chronic lymphocytic leukemia (CLL).

When determining whether to give a patient with CLL a BTK inhibitor alone or in combination with a CD20-directed antibody, it is important to have a discussion with patients, says Awan. During that conversation, the first question that is considered has to do with what benefit the patient can potentially derive from the addition of the CD20-directed antibody to the BTK inhibitor. Early data indicate that, at least with the addition of rituximab (Rituxan) to ibrutinib (Imbruvica), outcomes were not necessarily better than those observed with ibrutinib alone, says Awan. It should not be automatically assumed that the addition of a CD20-directed antibody to a BTK inhibitor will lead to longer remissions for patients, adds Awan.

In contrast, data from the CLL11 trial showed that obinutuzumab (Gazyva) outperformed rituximab, says Awan. As such, examining combinations with obinutuzumab made sense to examine in a clinical trial. Some emerging data suggest that there might be a trend toward improved outcomes when obinutuzumab is combined with acalabrutinib (Calquence) and possibly with ibrutinib. The field does not have the right trials to answer that specific question yet, concludes Awan.

Farrukh Awan, MD, discusses remaining questions regarding the use of BTK inhibitors and CD20-directed monoclonal antibodies in chronic lymphocytic leukemia.

Dr. Awan on Remaining Questions With BTK Inhibitors and Anti-CD20 Combos in CLL

Srikanth Nagalla, MD, director of the Hematology Oncology Fellowship Program at Harold C. Simmons Comprehensive Cancer Center, and associate professor of medicine at UT Southwestern Medical Center, discusses efforts to predict which patients with myeloproliferative neoplasms will develop thrombosis.

Similar to other diseases, investigators are working on putting together an algorithm to predict what patients with MPNs are going to develop thrombosis, says Nagalla. If the risk of developing thrombosis can be predicted, that could prevent unnecessary use of certain drugs.

Investigators are not only examining clinical factors; they are also looking at next-generation sequencing data as a way to identify genes that are being overexpressed or under expressed to see whether that can be used to predict which patients with a particular cancer might develop thrombosis. As science continues to evolve, investigators might be able to do a better job of predicting which patients are at risk of recurrent clots and be able to treat them accordingly with better drugs that have lower rates of bleeding, concludes Nagalla.

Dr. Nagalla on Efforts to Predict Risk of Thrombosis in Patients With MPNs

Syed Rizvi, MD, an assistant professor in the Department of Internal Medicine at UT Southwestern Medical Center, discusses the limitations of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in Hodgkin lymphoma.

ABVD has been a standard of care for patients with Hodgkin lymphoma for many years, explains Rizvi.

However, around 30% of patients do not respond to ABVD and require an alternative treatment strategy, says Rizvi.

Early identification of patients who are unlikely to respond to ABVD will help optimize patients’ treatment, says Rizvi.

Moreover, developing refined therapies that elicit extended progression-free survival and overall survival should remain an area of ongoing research in Hodgkin lymphoma, concludes Rizvi.

Syed Rizvi, MD, discusses the limitations of doxorubicin, bleomycin, vinblastine, and dacarbazine in Hodgkin lymphoma.

Dr. Rizvi on the Limitations of ABVD in Hodgkin Lymphoma

Ankit Kansagra, MD, assistant professor in the Department of Internal Medicine at Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses updates with CAR T-cell therapy in multiple myeloma.

The phase Ib/II CARTITUDE-1 trial sought to characterize the safety of JNJ-4528 and establish the recommended dosage. Results showed that the BCMA-directed CAR T-cell therapy achieved a 100% overall response rate (ORR) with early and deep responses in 29 patients with heavily pretreated relapsed/refractory myeloma at a median follow-up of 6 months. The ORR consisted of a 66% stringent complete response (CR) rate, a 3% CR rate, a 17% very good partial response (PR) rate, and a 14% PR rate.

Data have also been reported with the CAR T-cell therapy idecabtagene vicleucel (ide-cel; bb2121), which is, to some extent, a similar product. However, ide-cel has the potential to be given in an outpatient setting, depending on the cytokine release or the toxicity that occurred.

Moreover, even with a lower dose, good efficacy is being reported with this therapy, says Kansangra. It is difficult to compare 2 different products, but investigators are seeing how this construct was made and they might be able to achieve very good efficacy as it is examined further in trials, concludes Kansagra.

Ankit Kansagra, MD, discusses updates with CAR T-cell therapy in multiple myeloma.

Dr. Kansagra on Updates With CAR T-cell Therapy in 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 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.

UT Soutwestern

Dr. Kansagra on Updates With CAR T-Cell Therapy in Hematologic Cancers

Dr. Patel on the Clinical Implications of Luspatercept Approval in MDS

Dr. Patel on the Clinical Implications of Luspatercept Approval in MDS

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

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

Dr. Awan on Remaining Questions With BTK Inhibitors and Anti-CD20 Combos in CLL

Dr. Nagalla on Efforts to Predict Risk of Thrombosis in Patients With MPNs

Dr. Rizvi on the Limitations of ABVD in Hodgkin Lymphoma

Dr. Kansagra on Updates With CAR T-cell Therapy in Myeloma

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