Jonathan E. Brammer, MD

Jonathan E. Brammer, MD, assistant professor, internal medicine, The Ohio State University Comprehensive Cancer Center—James, discusses data that have been reported with inotuzumab ozogamicin (Besponsa) in acute lymphoblastic leukemia (ALL).

Inotuzumab ozogamicin is an antibody-drug conjugate that targets CD22, which is present on B-cell ALL cells.

The phase 3 INO-VATE study showed that 80% of patients who received inotuzumab ozogamicin achieved remissions compared with 30% of those who received standard chemotherapy. However, these remissions are generally short-lived, says Brammer. It is an effective agent, but it should be considered a bridge to transplant.

In terms of adverse effects, inotuzumab ozogamicin is associated with veno-occlusive disease. In the INO-VATE trial, 14% of patients had veno-occlusive disease. Therefore, chemotherapy agents that are known to induce veno-occlusive disease, such as busulfan, should be avoided when using this drug, says Brammer.

Although blinatumomab (Blincyto) could be used as an alternative agent to avoid the potential complication of busulfan, both drugs are recommended in National Comprehensive Cancer Network guidelines as bridges to transplant, concludes Brammer.

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Jonathan E. Brammer, MD, discusses data that have been reported with inotuzumab ozogamicin (Besponsa) in acute lymphoblastic leukemia (ALL).

Dr. Brammer on Data With Inotuzumab Ozogamicin in ALL

Jonathan E. Brammer, MD, assistant professor, internal medicine, The Ohio State University Comprehensive Cancer Center—–James, discusses the role of stem cell transplant in acute lymphoblastic leukemia (ALL).

Historically, the utility of allogeneic stem cell transplant (ASCT) in ALL was debated because its impact on survival was unknown, explains Brammer.

However, a study led by Nathalie Dhédin, MD, which evaluated two prospective clinical trials—–(NCT00222027) and (NCT00327678)––demonstrated a survival benefit with ASCT in patients who do not achieve minimal residual disease (MRD) negativity following treatment. Notably, the benefit was reported regardless of ALL subtype, says Brammer.

Patients who are MRD negative after chemotherapy and who do not have a high-risk subtype of ALL may not need transplant, says Brammer. However, patients should be counseled on an individualized basis to determine the optimal treatment strategy.

Notably, stem cell transplant has become safer and more effective for older patients with ALL. Historically, only patients ≤60 years old were considered transplant eligible. With reduced intensity conditioning, patients up to 75 years old may be eligible for transplant, says Brammer.

Finally, improved techniques have made it possible to use mismatched donors for some patients, concludes Brammer.

Jonathan E. Brammer, MD, discusses the role of stem cell transplant in acute lymphoblastic leukemia.

Dr. Brammer on the Role of Stem Cell Transplant in ALL

Jonathan E. Brammer, MD, assistant professor, internal medicine, The Ohio State University Comprehensive Cancer Center—–James, discusses the progression of transplant in acute lymphoblastic leukemia (ALL).

Traditionally, stem cell transplant (SCT) was indicated for patients with Philadelphia chromosome—positive disease or who failed to attain a remission; however, over time the patient populations eligible for SCT has changed as more differentiated subtypes and high-risk groups were identified, explains Brammer. Additionally, more effective therapies have emerged, making SCT less necessary.

Patients with minimal residual disease—positive disease after induction or at the end of treatment appear to derive more benefit from transplant, whether or not they receive salvage therapy, says Brammer. Without SCT, those patients will likely relapse. SCT should also be considered in patients with high-risk ALL, including early T-cell precursor ALL, mixed-lineage ALL, and Philadelphia-like ALL, concludes Brammer.

Jonathan E. Brammer, MD, discusses the progression of transplant in acute lymphoblastic leukemia.

Dr. Brammer on the Transformation of Stem Cell Transplant in ALL

Jonathan E. Brammer, MD, assistant professor, internal medicine, The Ohio State University Comprehensive Cancer Center—–James, discusses the importance of achieving minimal residual disease (MRD) negativity in relapsed/refractory acute lymphoblastic leukemia (ALL).

MRD is an important predictor of outcomes in both B-cell ALL and T-cell ALL, says Brammer. The majority of patients who are MRD positive after induction chemotherapy will relapse.

The phase II BLAST study evaluated the bispecific T-cell engager blinatumomab (Blincyto). The drug received regulatory approval in 2018 for the treatment of adult and pediatric patients with MRD-positive B-cell precursor ALL. The study confirmed that blinatumomab is effective in eradicating MRD in patients who received at least 3 cycles of prior treatment. Notably, many of these patients were subsequently eligible to receive stem cell transplantation, concludes Brammer.

Jonathan E. Brammer, MD, discusses the importance of achieving minimal residual disease negativity in relapsed/refractory acute lymphoblastic leukemia.

Author | Jonathan E. Brammer, MD

Articles

Dr. Brammer on Data With Inotuzumab Ozogamicin in ALL

Dr. Brammer on the Role of Stem Cell Transplant in ALL

Dr. Brammer on the Transformation of Stem Cell Transplant in ALL

Dr. Brammer on the Importance of MRD in Relapsed/Refractory ALL