Three August Blood Cancer Approvals and What They Mean for Care

September is Blood Cancer Awareness Month, and recent weeks have brought major changes for people with blood cancers. In August, the FDA approved three treatments: Zenbexus (iberdomide) for relapsed multiple myeloma, Mimrylo (rusfertide) for polycythemia vera and Besremi (ropeginterferon alfa-2b-njft) for essential thrombocythemia.

To explain what these approvals and other recent advances mean for people with blood cancers, CURE spoke with Dr. Guenther Koehne. He is deputy director and chief of blood and marrow transplant, hematologic oncology and benign hematology at Baptist Health Herbert Wertheim Cancer Institute in Miami. In part 1 of this two-part interview, Dr. Koehne covers the August approvals, how doctors choose first-line treatment for multiple myeloma and what it means to be MRD negative.

Transcript has been edited for clarity and conciseness.

Which of the August blood cancer approvals will change care the most?

August brought three blood cancer approvals: Zenbexus for relapsed myeloma, Mimrylo for polycythemia vera and Besremi for essential thrombocythemia. Which of these changes care the most, and who should be asking about them?

All three are recent FDA approvals. I think the most impactful will be the first one you mentioned, Zenbexus, or iberdomide. Other drugs have already been approved for the treatment of multiple myeloma, and I think this one will have an impact on the treatment of relapsed multiple myeloma. It may also help support immunotherapies. We'll talk about CAR T-cell therapies and bispecific antibody therapies later on.

Iberdomide belongs to a group of drugs called CELMoDs. A CELMoD like iberdomide enhances immune function, and with that, the duration of the T cells. I believe that in the future it will be combined with CAR T cells to enhance their proliferation and duration, and maybe similarly with bispecific antibodies. Right now, it has been approved in combination with Darzalex (daratumumab). The right timing for this treatment still needs to be determined. It will not be up front; it will be for later-line treatment of multiple myeloma.

Mimrylo, or rusfertide, is a new drug for the treatment of polycythemia vera, a myeloproliferative disorder. It reduces the uptake of iron into red cells, which is part of how polycythemia vera develops. That makes it another alternative to the current standard of care. In the early stages, the standard of care is phlebotomy, which means frequent blood draws to reduce the red cell mass. This drug has shown potential to reduce the number of phlebotomies needed, so it is very promising from that perspective.

The final one you mentioned, Besremi, is an interferon alfa drug that is not that new. It has been approved for polycythemia vera and now also for essential thrombocythemia. Both are myeloproliferative disorders, so we now have an additional treatment option for people with these diseases.

It's worth pointing out that these drugs have been approved and they are effective, but they are also associated with side effects. They will not necessarily be a curative approach. Stem cell transplantation will remain the curative treatment approach for people with myeloproliferative disorders.

Why MPN treatment decisions must be individualized

On the question of which patient should get which treatment, the answer clearly is that it has to be individualized. If you are 80 years old and have polycythemia vera or essential thrombocythemia, you will likely be happy to use these drugs for as long as possible and for as long as they are tolerated. If you are 50 years old, you may not want to be exposed to these drugs for the rest of your life. In fact, they may not be effective for the rest of your life. That's why allogeneic donor stem cell transplantation will still be the curative approach for myeloproliferative disorders such as polycythemia vera or essential thrombocythemia.

How is first-line treatment chosen for newly diagnosed multiple myeloma?

How do you decide what a person with newly diagnosed multiple myeloma gets first, and how does that change what's left for later?

The standard treatment for newly diagnosed multiple myeloma has changed. Those of us in the field now agree that quadruplet therapy is the accepted standard for starting treatment. Quadruplet means four drugs, including daratumumab. That can be dara-RVd, which is Revlimid (lenalidomide), Velcade (bortezomib) and dexamethasone. It can also be dara-KPd, which is Kyprolis (carfilzomib), Pomalyst (pomalidomide) and dexamethasone.

Right now, everyone should get a quadruplet initial therapy based on risk stratification. People with standard-risk multiple myeloma can get the somewhat milder dara-RVd. Those with high-risk cytogenetics should be treated with dara-KPd unless there are reasons they cannot receive these drugs.

That is a change. Years ago, daratumumab came later in treatment. Now it's clear that quadruplet therapy including daratumumab should be used to start treatment and get patients into complete remission.

Then the question is what comes next. Usually, if patients are in remission, they will have an autologous stem cell transplant followed by maintenance therapy.

Where do bispecific antibodies fit in myeloma treatment?

Tecvayli (teclistamab) brings us to where we are today with multiple myeloma treatment, and these are all immunotherapy-directed treatments. Teclistamab is a bispecific antibody that binds to a marker called BCMA, or B-cell maturation antigen, on the myeloma cell. In doing so, it attracts the patient's own T cells to the site of the myeloma. There are other bispecific antibodies as well, such as Elrexfio (elranatamab). They are used later on, as second- or third-line treatment, for people with relapsed multiple myeloma or those who do not reach a deep molecular remission.

That is the new development, and it is an exciting time for patients and physicians. There are many developments in multiple myeloma treatment, and they are all moving in the direction of immunotherapy. In fact, chemotherapy will rarely be given, except before an autologous stem cell transplant. With CAR T cells and bispecific antibodies, we are for the first time really talking about a potential cure for people with multiple myeloma, which has never been the case before.

What does it mean to be MRD negative?

Where does MRD testing fit into how you track blood cancers today, and what should a patient understand if they hear they are MRD negative?

MRD stands for measurable residual disease, previously called minimal residual disease, and both terms are still used. Being MRD negative means that a patient is in a very deep molecular remission. We now have very sensitive tests, like clonoSEQ and other molecular testing. These tests can detect single remaining clones of disease hidden somewhere in the bone marrow or blood.

We know that when a patient becomes MRD negative, the remission lasts longer. That may also reduce the amount of treatment needed afterward, so it really affects treatment options and maintenance approaches. The tests we had before, such as flow cytometry, were less sensitive. With this high level of sensitivity, we can detect much deeper remissions, maybe even a situation where we can say it's curative. We are very careful using the word cure in multiple myeloma and leukemia.

How MRD status guides blood cancer treatment decisions

In hematologic malignancies such as acute lymphoblastic leukemia, lymphoma, acute myeloid leukemia and multiple myeloma, treatment is directed by MRD status. Can we stop treatment if a patient is MRD negative, or should we continue if they are still MRD positive? And what do we do if a patient goes from MRD negative back to MRD positive after treatment has stopped or after a stem cell transplant? Because MRD testing is so sensitive, we are now able to intervene at an earlier point in hematologic malignancies.

Stay tuned for part 2, where Dr. Koehne explains the differences between CAR T-cell therapy and bispecific antibodies, the role of transplant in 2026 and what people with myeloproliferative neoplasms can expect in the years ahead.

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