Double Stem Cell Transplant Feasible for Some With Multiple Myeloma

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One expert explains why double autologous stem cell transplantation is a viable alternative to back-to-back transplant in high-risk multiple myeloma.

Double autologous stem cell transplantation (ASCT) is a feasible treatment approach for patients with high-risk (HR), transplant-eligible (TE), newly diagnosed multiple myeloma (NDMM), according to recent research published in the journal, Blood.

The team of researchers enrolled 50 patients with previously untreated, newly diagnosed multiple myeloma, with treatment scheduled to include induction therapy with Darzalex (daratumumab), Kyprolis (carfilzomib), Revlimid (lenalidomide) and the steroid dexamethasone — a regimen referred to as D-KRd — followed by ASCT, D-KRd consolidation, a second ASCT, and Darzalex-Revlimid maintenance therapy.

Dr. Rahul Banerjee, assistant professor in the Division of Hematology and Oncology at the University of Washington, assistant professor in the Clinical Research Division of the Fred Hutchinson Cancer Center and co-author of a commentary article published alongside the study in Blood, mentioned that breaking up the transplants with consolidation therapy may be a more tolerable approach than the traditional method of receiving back-to-back transplants.

Autologous stem cell transplantation, according to the National Cancer Institute, is when a patient’s healthy blood-forming stem cells are collected prior to treatment and then given back following treatment to replace cells destroyed in the cancer treatment process.

Darzalex targets the CD38 protein on cancer cells to help destroy cancer, while Kyprolis inhibits an enzyme called proteasome, which prevents the growth of cancer cells while killing them, according to the National Cancer Institute.

At a median follow-up of 33 months, the 30-month progression-free survival (the time a patient lives without their disease spreading or worsening) and overall survival (OS; the time a patient lives regardless of disease status) rates were 80% and 91%, respectively.

The overall response rate (patients whose disease responded partially or completely to treatment) was 100% among patients who completed second transplant, with 81% experiencing a complete response (disappearance of cancer). Meanwhile 94% achieved minimal residual disease negativity (the absence of small amounts of malignant cells detected via blood test) before maintenance therapy.

As of the study’s data cutoff, 36 patients had completed second transplant, and 20 patients had discontinued the study due to stem collection failure (eight patients), disease progression (seven patients), side effects (four patients) or withdrawal of consent to participate in the study (one patient).

Researchers reported that grade 3 (severe) or 4 (life-threatening) induction and consolidation-related side effects in at least 5% of patients included neutropenia (low neutrophils, a type of white blood cell; 39%), anemia (low red blood cells; 12%), thrombocytopenia (low platelets; 7%) and infection (6%).

Banerjee discussed these findings and what they mean for patients.

Transcript:

What is very unique about this study is that there was a time when we used to use tandem transplant, which is true back-to-back stem cell transplantation [with] high-dose chemotherapy for our patients. And it is really tough. We used to end up putting patients in a very difficult situation where we would recommend a tandem transplant, and … a lot and patients would feel very guilty about saying no to that, because they just didn't want to deal with that quality of life hit, just to add some context.

With the high-dose chemotherapy and autologous stem cell rescue, also known as autologous stem cell transplant, we give patients a high-dose of chemo, that true chemotherapy that they haven't typically received before, that wipes out the bone marrow — everything it sees, good and bad, it destroys. We’ve pre-collected their healthy stem cells, and we give it back to them. I typically tell patients to expect at least two to three weeks of misery, about two to three months of functional recovery, and typically about two to three years of benefit, of added remission that you would not expect otherwise, with the addition of this transplant. It’s a lot for patients. Most of my patients who are eligible for transplant go through with transplant and they come out of it and they do not want to undergo that again. I say, “I understand, you've done your time, you've done your investment, this transplant will hopefully add an extra, again, two to three years’ worth of remission that we wouldn't otherwise have seen, onto the next and best available treatment, when that day becomes pertinent down the future.”

[To] tandem the transplant is tough, because then we’re saying, “Look, as soon as you are feeling better again, as soon as a day is starting to pass [when there are] more days … that you don't remember that you just had your bone marrow reset, boom, we do it all over again.”

Historically, in the BMT CTN 0702 study, it was the STaMINIA study, a big trial of single transplant versus tandem transplant versus adding targeted therapy after transplant, and 20%, 30%, if I recall correctly, of the patients who were in the tandem transplant arm did not undergo transplant. So, they were assigned to undergo two transplants. But when it actually came down to it, they said, “Look, I would rather just not. I can't fathom having this happen to me again,” [with] what they've been through.

And so tandem transplant, I do think it adds some benefit, to do two transplants has some benefit to myeloma. But the back-to-back [approach] is really too much for patients. So, I think what’s really innovative about this study — and it’s confusing, the word, the title of the study and what we're describing is confusing, I wouldn't really call it tandem transplant, I would call it double transplant. There is a key thematic difference here. It’s not tandem, not back-to-back, it’s not that our patient is being asked to go right back to transplant, right back to losing their hair or being hospitalized, feeling miserable as soon as they’re feeling better. They get better after transplant, we know that they have high-risk disease, we give them some cycles of what they were getting before, and then we go back to transplant thereafter. That, I think, is what's innovative about the study.

[The researchers] only did it for high-risk patients. So again, all these patients where we know that a single transplant doesn't historically add the value that we would like it to add, how can we augment it? There have been a plethora — at least a dozen — approaches I can think of that have been approached to handle patients with high-risk cytogenetics. This is a newer tool in the toolbox, where if someone wants to undergo second transplant, just not now, they're just recovering, they want to rebuild their life a little bit. That is reasonable and this study provides a pathway to do that.

Transcript has been edited for clarity and conciseness.

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