Rami Komrokji, MD, vice chair, Malignant Hematology Department, head, Leukemia and MDS Section, Moffitt Cancer Center, senior member, Malignant Hematology and Experimental Therapeutics Program, professor, Medicine & Oncologic Sciences, College of Medicine, the University of South Florida, discusses the benefit of agents such as luspatercept-aamt (Reblozyl) in patients with very low– to intermediate-risk myelodysplastic syndromes (MDS) who have not received prior treatment with erythropoiesis-stimulating agents (ESAs).

 for patients with lower-risk MDS with anemia requiring transfusions, he begins. There's a push to consider initiating treatment for patients experiencing symptomatic or significant anemia before the necessity for blood transfusions arises, Komrokji states. The forthcoming phase 3 ELEMENT-MDS study (NCT05949684), which follows the pivotal phase 3 COMMANDS trial (NCT03682536), is specifically designed to investigate this, he says. ELEMENT-MDS intends to focus on patients not in need of blood transfusions and randomly assign them to receive either ESA agents or luspatercept. The goal of the trial is to gather data to support the transition toward treating patients with symptomatic or significant anemia before they require transfusions, Komrokji emphasizes.

Currently, the role of luspatercept in MDS is evolving. Most guidelines suggest its use as a primary treatment option for patients requiring blood transfusions because it has doubled response rates and increased response duration in this subset of patients, Komrokji expands. However, the generalization of these data to patients whose MDS does not have ring sideroblasts (MDS-RS) or is lacking the 

 mutation is debated, he notes. The responses observed with luspatercept in patients without ring sideroblastic disease are similar to those seen with ESA therapies in this population. Yet, specific subsets of patients, especially those anticipated to have a low likelihood of responding to an ESA, may benefit from luspatercept, and the current indication for this agent includes these patients, Komrokji notes.

There's an ongoing effort to explore other disease factors that may favor the use of luspatercept over ESAs, such as baseline mutation burden or specific mutations, he continues. Presently, the consensus is leaning toward using luspatercept as the preferred first-line treatment for all patients with MDS-RS, and as a possible first-line choice for select patients without MDS-RS, Komrokji says. Future research in this area aims to advance treatment strategies so patients can receive therapy before the necessity for blood transfusions, Komrokji concludes.

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Rami Komrokji, MD, discusses the benefit of agents such as luspatercept-aamt in patients with very low– to intermediate-risk myelodysplastic syndromes who have not received prior treatment with erythropoiesis-stimulating agents.

Dr Komrokji on Ongoing Investigations With Luspatercept in MDS

Rami S. Komrokji, MD, principal investigator, MDS Research Consortium, Aplastic Anemia and MDS International Foundation, clinical director, Hematologic Malignancies, Moffitt Cancer Center, discusses the changing landscape of acute myeloid leukemia (AML).

Physicians have made tremendous therapeutic strides for patients with AML, explains Komrokji. In the past year, the field has seen several FDA approvals. Data have shown that younger patients with good-risk disease and t(8;21) or inversion 16 seem to derive the most benefit from the incorporation of a lower dose of gemtuzumab ozogamicin (Mylotarg) into induction and consolidation. Now, it is becoming a part of the standard of care for these patients, says Komrokji.

 mutations, the incorporation of midostaurin (Rydapt) with a chemotherapy backbone has become the standard of care. This regimen has demonstrated a benefit in overall survival. Historically, getting this information in a fast-enough turnaround time was a difficulty. Now, the academic centers and the labs that perform those tests have a rapid turnaround time of a few days, notes Komrokji.

Dr. Komrokji on the Changing Landscape of AML

Rami S. Komrokji, MD, Principal Investigator, MDS Research Consortium, Aplastic Anemia and MDS International Foundation, clinical director, Hematologic Malignancies, Moffitt Cancer Center, discusses molecular testing for patients with myelodysplastic syndromes (MDS).

Molecular testing in these patients has been done for many years at diagnosis and now it is important to look at next-generation sequencing to investigate the somatic gene mutations, explains Komrokji.

With the integration of somatic gene mutations, abnormalities can be identified in 80% to 90% of the patients, states Komrokji.

Rami S. Komrokji, MD, clinical director, Hematologic Malignancies, Moffitt Cancer Center, discusses molecular testing for patients with myelodysplastic syndromes (MDS).

Dr. Komrokji Discusses Molecular Testing for MDS

Rami S. Komrokji, MD, clinical director, Department of Malignant Hematology, H. Lee Moffitt Cancer Center, discusses a study that examined risk stratification of therapy-related MDS.

Komrokji said for the study, 370 patients with therapy-related MDS were compared to a cohort of patients with de novo MDS. Half of the patients with therapy-related MDS had solid tumors and the majority were treated with chemotherapy for their prior disease. The results showed that most of the clinical models do predict the outcome of these patients.

From this study, researchers found that if you take a patient with de novo MDS and compare them stage-by-stage with therapy-related MDS, patients with therapy-related MDS always do worse, even if the disease is classified as low-risk therapy-related MDS, Komrokji says. However, there is a subset of patients whose survival can be measured in years. These patients could be treated stepwise as opposed to treating them as high-risk, Komrokji says.

The results found that the revised IPSS and the Global MD Anderson Model were the best models to estimate outcome in therapy-related MDS patients. Komrokji says the next step to risk stratifying these patients would be integrating the molecular mutations in patients with therapy-related MDS.

Dr. Komrokji on Risk Stratification of Therapy-Related MDS

Rami S. Komrokji, MD, clinical director, Hematologic Malignancies, Moffitt Cancer Center, discusses optimizing the management of treatment for myelodysplastic syndrome (MDS).

Because there are limited options approved for MDS, it is important that oncologists optimize treatment in order to achieve the best results, says Komrokji.

Biomarkers can be used to best select which treatment should be used first for MDS. It is also important to be familiar with the management, toxicities and response timelines for each treatment. This way, if a treatment is not working well, the physician can switch to a more optimal treatment regimen.

Komrokji says it is also important to determine the optimal time, if at all, to conduct a transplant. â€‹

Dr. Komrokji on Optimizing MDS Management

Rami S. Komrokji, MD, clinical director, Hematologic Malignancies, Moffitt Cancer Center, discusses the risk factors of developing myelodysplastic syndromes (MDS) and any preventative measures.

It is unclear why the majority of patients develop MDS, Komrokji says. It is thought to be a process of aging and various environmental factors. There are some genetic components linked to MDS; however, they are rare. If there is a significant family history of MDS, Komrokji recommends patients have their blood counts monitored regularly.

In terms of long-term exposure, Komrokji says environmental or industrial chemicals such as benzene may trigger MDS. One of the sources of benzene exposure is tobacco use, he adds, leading there to be some association between tobacco and MDS. Possible preventative measures include regular exercise, a balanced diet, and no smoking.

MDS can also be discovered when a patient is receiving chemotherapy or radiation for another disease, Komrokji says. It’s a possibility this could be due to stem cell damage; however, patients could also have predisposition, such as small clones of a p53 mutation.

If these patients can be better identified in the future, Komrokji hopes that their therapies can be better tailored to avoid treatments that could trigger MDS. 

Rami S. Komrokji, MD, clinical director, Hematologic Malignancies, Moffitt Cancer Center, discusses the risk factors of developing myelodysplastic syndromes (MDS) and any preventative measures.


Dr. Komrokji on MDS Risk Factors and Preventative Measures

Rami S. Komrokji, MD, clinical director, Hematologic Malignancies, Moffitt Cancer Center, discusses an analysis of pacritinib for the treatment of myelofibrosis.

Currently, only one JAK2 inhibitor, ruxolitinib, is approved for the treatment of myelofibrosis, though several others are being investigated. Pacritinib, a dual JAK2/FLT3 inhibitor, was looked at in an integrated analysis from 2 phase I/II clinical trials. Databases from the trials in advanced myeloid malignancies and myelofibrosis evaluated the rate of adverse events and favorable spleen responses in patients with myelofibrosis and thrombocytopenia.

Komrokji says thrombocytopenia occurs in about one-third of patients with myelofibrosis and is associated with poor outcomes. A limitation of many new JAK2 inhibitors is myelosuppression.

This integrated analysis found that pacritinib was well tolerated with no instances of major adverse events in myelofibrosis, regardless of a patient’s baseline platelet counts.

Rami S. Komrokji, MD

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