2025 Leukemia and Lymphoma Updates: Clarkson’s Disease, Myeloma, and MDS Treatments
The field of hematology is witnessing remarkable advancements, offering new hope for patients with rare blood disorders and cancers. In a recent discussion hosted by the Medical Oncology Association of Southern California (MOASC) as part of the 2025 Leukemia / Lymphoma Updates, Dr. Aaron Goodman, MD, from UC San Diego, provided an in-depth look at Clarkson’s disease, relapsed diffuse large B-cell lymphoma (DLBCL), multiple myeloma, and low-risk myelodysplastic syndromes (MDS). This comprehensive session highlighted the latest treatment options, their challenges, and the importance of patient-centered care in navigating these complex conditions.
What Is Clarkson’s Disease? Understanding a Rare Monoclonal Gammopathy
Clarkson’s disease, also known as systemic capillary leak syndrome, is a rare monoclonal gammopathy with significant clinical implications. Patients often present with recurrent episodes of shock and hypotension, yet there’s no obvious trigger—no infections, no allergies. Dr. Goodman explained that all patients with Clarkson’s disease, by definition, have a paraprotein—a monoclonal protein in their blood—identified through serum protein electrophoresis (SPEP) and immunofixation. This incredibly rare condition has limited treatment data, primarily derived from case reports and small case series.
Symptoms and Diagnosis of Clarkson’s Disease: What to Know
The hallmark of Clarkson’s disease is its sudden onset of hypotensive shock without a clear cause. Patients do not exhibit signs of infection or allergic reactions, making diagnosis challenging. The presence of a monoclonal protein, detected through SPEP and immunofixation, is a defining feature, helping clinicians differentiate it from other conditions with similar presentations.
Clarkson’s Disease Treatment Options: From IVIG to Myeloma Drugs
Despite its rarity, a key insight is that therapies targeting myeloma can be effective for Clarkson’s disease. Drugs like IVIG (intravenous immunoglobulin) are typically the first line of treatment, administered monthly. If IVIG fails, immunomodulatory agents such as Revlimid, Velcade, or other proteasome inhibitors can be used to target the clone secreting the monoclonal protein, offering a potential path to remission.
Relapsed DLBCL Treatment: CAR-T Cell Therapy vs. Bispecific Antibodies
For patients with multiply relapsed DLBCL, the treatment landscape has expanded significantly. Dr. Goodman emphasized the role of advanced therapies in improving outcomes for these patients.
CAR-T Cell Therapy for DLBCL: Cure Rates and Eligibility
CAR-T cell therapies have a proven track record with longer follow-up data. “We’re curing roughly 30 to 40% of those patients,” Dr. Goodman noted, making CAR-T a preferred option when patients are eligible. However, the process to determine candidacy for CAR-T is lengthy and involves assessing the patient’s overall health and ability to withstand the treatment’s risks.
Bispecific Antibodies in DLBCL: Benefits and Challenges
For those who are not candidates for CAR-T—due to age, comorbidities, or personal preference—bispecific antibodies offer an alternative. While bispecifics have a good track record, their long-term follow-up data is less robust, and Dr. Goodman cautioned that they don’t yet promise a cure. Still, they can provide long-term durable remissions, though they require continuous infusions. This can pose logistical challenges for patients living far from cancer centers, though more community centers are beginning to administer bispecifics after the initial treatment phase at a university hospital.
Relapsed Multiple Myeloma: CAR-T Cells, Bispecifics, and More
The treatment of relapsed multiple myeloma has also seen a “bounty of choices,” according to Dr. Goodman, providing new avenues for managing this challenging disease.
Cilta-Cel and CAR-T Therapy for Myeloma: What to Expect
CAR-T cell therapies like cilta-cel (Carvykti) are favored for eligible patients, offering remissions that can last years. Unlike in DLBCL, CAR-T cells in myeloma are not curative, but they provide a significant break from continuous therapy for patients who have been on treatment for extended periods. Patients can expect a rigorous evaluation process to determine eligibility, followed by a recovery period that may lead to extended remission.
Bispecific Antibodies for Myeloma: Talquetamab and Teclistamab
For those who relapse after CAR-T or are not candidates, bispecific antibodies like talquetamab (which targets a different protein than cilta-cel) and teclistamab (targeting BCMA) are viable options. Dr. Goodman outlined a strategic approach: using talquetamab after cilta-cel, and if that fails, switching to another bispecific like teclistamab. For patients who opt out of CAR-T, bispecifics are often the first line of treatment, providing flexibility in managing this disease.
Low-Risk MDS: New Therapies to Reduce Transfusion Dependence
Low-risk myelodysplastic syndromes (MDS) have historically been difficult to treat, with patients often relying on transfusion support. However, recent FDA approvals have introduced new options.
Luspatercept for MDS: Improving Anemia in Low-Risk Patients
Dr. Goodman highlighted luspatercept, an infusion therapy initially approved for MDS patients with ring sideroblasts or SF3B1 mutations but now approved for all low-risk MDS. It works by improving anemia, raising hemoglobin levels in about half of patients, and reducing the need for transfusions. While it’s generally well-tolerated, some patients experience infusion-related reactions.
Imetelstat in MDS: A New Option After Other Treatments Fail
Imetelstat, often used after erythropoiesis-stimulating agents and luspatercept fail, also aims to improve anemia but comes with side effects like low platelets and potential liver irritation. These therapies mark a significant step forward, offering patients alternatives to continuous transfusions and improving their quality of life.
Blood Cancer Treatment Challenges: Side Effects, Costs, and Access
The rapid pace of FDA approvals in blood cancer treatment—sometimes monthly, as Dr. Goodman noted—is undeniably good news for patients. From CAR-T cells to bispecifics to novel drugs like luspatercept, the options are expanding, offering hope where there was once little.
Financial and Time Toxicity in Blood Cancer Therapies
However, these advancements come with significant challenges. Many of these therapies carry “financial toxicity” due to their high costs and “time toxicity” from frequent hospital visits. For example, bispecifics’ need for continuous infusions can be a barrier for patients living far from treatment centers.
Managing Side Effects of Advanced Blood Cancer Treatments
Side effects can also impair quality of life. Drugs like imetelstat require careful monitoring for issues like liver irritation, while CAR-T therapies can pose risks that need to be weighed against their benefits. Dr. Goodman stressed the importance of transparency with patients about these potential challenges.
The Future of Blood Cancer Care: Innovation and Patient-Centered Decisions
As the treatment landscape grows more complex, the future of blood cancer care hinges on balancing innovation with practicality.
Why Informed Discussions Matter for Blood Cancer Patients
“It’s good to have a lot of options, but it can make it very difficult to have these discussions,” Dr. Goodman said. Patients need to understand not only the potential benefits of these therapies but also the risks and trade-offs. For healthcare providers, the challenge lies in tailoring treatments to each patient’s unique circumstances—considering factors like age, comorbidities, and proximity to care—while keeping up with the latest research.
MOASC 2025: Leading the Way in Leukemia and Lymphoma Research
Events like MOASC’s 2025 Leukemia / Lymphoma Updates provide a critical platform for sharing knowledge and fostering collaboration among healthcare professionals. For patients, staying informed about these advancements can empower them to make the best decisions for their care. Watch the full discussion [insert link] to dive deeper into these groundbreaking therapies, and join the conversation about the future of hematology.
Related Links:
https://providers.ucsd.edu/details/32771/cancer-blood-&-marrow-transplant-bmt-medical-oncology
