Omar Alkharabsheh, MD, a medical oncologist and hematologist, and an assistant professor of Interdisciplinary Clinical Oncology at the USA College of Medicine, discusses remaining challenges in high-risk chronic lymphocytic leukemia (CLL).

Patients with CLL and high-risk cytogenetics, such as 17p deletion or complex karyotype, or who are resistant to BTK inhibitors represent a significant unmet need in CLL, says Alkharabsheh. Moreover, these patients have poorer outcomes vs the general CLL population, Alkharabsheh adds. 

Currently, allogeneic stem cell transplant is the standard of care for this patient population; however, only fit patients with donors are eligible to undergo transplant, Alkharabsheh. As such, novel therapies, such as CAR T-cell therapy, could provide an effective therapy that could induce remissions in patients with high-risk CLL, concludes Alkharabsheh.

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Omar Alkharabsheh, MD, discusses remaining challenges in high-risk chronic lymphocytic leukemia. 



Dr. Alkharabsheh on Remaining Challenges in High-Risk CLL 

Omar Alkharabsheh, MD, a medical oncologist and hematologist, and an assistant professor of Interdisciplinary Clinical Oncology at the USA College of Medicine, discusses ongoing research efforts examining combination therapies in patients with mantle cell lymphoma (MCL).

More data from trials with combination therapies in MCL are needed, such as BTK inhibitors and BCL-2 inhibitors, which have also been examined in trials for chronic lymphocytic leukemia, Alkharabsheh says. Additionally, investigators need to identify whether these combinations will elicit different responses and better outcomes in this population, Alkharabsheh explains.

However, combination regimens are not a one-size-fits-all approach due to the heterogeneous nature of MCL. If the patient has high proliferative disease, high Ki-67, or a blastoid disease variant, a chemotherapy-free regimen may require more time before inducing remission or control of the aggressive disease, Alkharabsheh says. 

Chemotherapy continues to exist as the backbone of treatment in MCL; however, it is important to understand which agents to combine, as well as the best strategy to combine them to achieve optimal responses and outcomes, Alkharabsheh concludes.

Omar Alkharabsheh, MD, discusses ongoing research efforts examining combination therapies in patients with mantle cell lymphoma.



Dr. Alkharabsheh on Ongoing Research Efforts Examining Novel Combos in MCL

Omar Alkharabsheh, MD, a medical oncologist and hematologist, as well as an assistant professor of Interdisciplinary Clinical Oncology at the USA College of Medicine, discusses emerging treatment options in chronic lymphocytic leukemia (CLL).

Currently, clinical trials and treatment options for patients with CLL are expanding, Alkharabsheh says. While multiple agents are available in the space, it is unknown which therapies are best, according to Alkharabsheh. Several recommendations exist within the National Comprehensive Cancer Network guidelines for both single-agent and combination strategies. This presents a challenge, as it is difficult to select 1 option with the intent of providing the best outcome, Alkharabsheh explains. 

Patients must be informed on all the available options and be matched to inclusion criteria of ongoing clinical trials, Alkharabsheh says. Many approaches exist, but it is important to identify the best one with the fewest adverse effects and potential complications, while also factoring in patient comorbidities, Alkharabsheh concludes.

Omar Alkharabsheh, MD, discusses emerging treatment options in chronic lymphocytic leukemia.

Dr. Alkharabsheh on Emerging Treatment Options in CLL

Omar Alkharabsheh, MD, assistant professor of interdisciplinary clinical oncology at USA College of Medicine and a medical oncologist and hematologist at USA College of Medicine, discusses future research directions for the treatment of patients with myeloproliferative neoplasms (MPNs).

Currently, many early-phase clinical trials are examining treatment options for patients with MPNs, such as myelofibrosis, Alkharabsheh says. For example, the BCL-2 inhibitor navitoclax is being combined with JAK inhibitors in this patient population, Alkharabsheh notes. Moreover, ruxolitinib (Jakafi) induces some suppression of the JAK/STAT pathway, which could lead to improvements in symptoms and reduction in spleen size, although it does not change the biology of the disease, Alkharabsheh explains.

By adding a BCL-2 inhibitor to ruxolitinib, it is believed that the disease biology can be changed by decreasing the risk of progression to acute myeloid leukemia (AML) and improving overall survival, according to Alkharabsheh. However, this regimen will need to be further investigated in a more advanced clinical trial, Alkharabsheh concludes.

Omar Alkharabsheh, MD, discusses future research directions for the treatment of patients with myeloproliferative neoplasms.

Dr. Alkharabsheh on Future Research Directions in MPNs

Omar Alkharabsheh, MD, an assistant professor of interdisciplinary clinical oncology at the USA College of Medicine, as well as a medical oncologist and hematologist with Mitchell Cancer Institute, USA Health, discusses novel agents in the field of myelofibrosis.

Ropeginterferon alfa-2b is now in development and is being explored in European clinical trials for patients with myelofibrosis, says Alkharabsheh. This agent was also compared with hydroxyurea in a phase 3 trial. Results showed durable responses and noninferior hematologic response with ropeginterferon alfa-2b; however, the agent was not able to induce a significant reduction in spleen size, adds Alkharabsheh.

Additionally, patients who progress on JAK2 inhibitors need to be treated in clinical trials, as there are still no acceptable options for them, adds 

 Most of those clinical trials require that participants have good platelet counts. Although after receiving a JAK2 inhibitor or upon disease progression, patients will often experience thrombocytopenia that limits their options in terms of clinical trials. 

The field has another JAK2 inhibitor called momelotinib (Inrebic), which is still in clinical trials, but the unique quality is that the drug demonstrated improvement with regard to anemia and reduced transfusion dependency in patients with myelofibrosis, concludes Alkharabsheh.

Omar Alkharabsheh, MD, discusses novel agents under exploration in the field of myelofibrosis.

Dr. Alkharabsheh on Novel Agents Under Exploration in Myelofibrosis

Omar Alkharabsheh, MD, assistant professor of interdisciplinary clinical oncology, USA College of Medicine, medical oncologist and hematologist, Mitchell Cancer Institute, USA Health, discusses the current goals of treatment in myeloproliferative neoplasms (MPNs).

In patients with essential thrombocythemia (ET) or polycythemia vera (PV), the goal of treatment is to decrease the risk of clotting, control cardiovascular risk factors such as hypertension, diabetes, and lipedema, and determine when to initiate antiplatelet or cytoreductive therapy, Alkharabsheh explains. 

Additionally, patients with ET or PV require close monitoring to identify whether their disease has progressed to myelofibrosis, adds Alkharabsheh.

The current standard of care for patients with ET or PV is cytoreduction with hydroxyurea, Alkharabsheh says.

JAK2 inhibitors do not change the biology of a patient’s disease by inducing complete remissions or molecular responses. However, the COMFORT-I and COMFORT-II trials demonstrated improvement in symptoms and splenomegaly with the JAK2 inhibitor ruxolitinib (Jakafi), concludes Alkharabsheh.

Omar Alkharabsheh, MD, discusses the current goals of treatment in myeloproliferative neoplasms.  


Omar Alkharabsheh, MD

Articles

Dr. Alkharabsheh on Remaining Challenges in High-Risk CLL

Dr. Alkharabsheh on Ongoing Research Efforts Examining Novel Combos in MCL

Dr. Alkharabsheh on Emerging Treatment Options in CLL

Dr. Alkharabsheh on Future Research Directions in MPNs

Dr. Alkharabsheh on Novel Agents Under Exploration in Myelofibrosis

Dr. Alkharabsheh on the Goals of Treatment in MPNs