Evaluating the Proximity and Impact of a Cure in Multiple Myeloma

According to Sundar Jagannath, MBBS, the cure for multiple myeloma was observed in patients who were cancer-free for 5 years without maintenance therapy.

At the Society of Hematological Oncology 2025 Annual Meeting, CancerNetwork® spoke with Sundar Jagannath, MBBS, about his presentation on potentially defining a cure in the therapy of patients with multiple myeloma.¹

Not only will being able to tell patients they have the possibility of being cured have a significant effect on their sense of hopefulness, a cure will also modify the way that physicians and pharmaceutical companies approach their treatment strategies and therapy development.

Results from the phase 1b/2 CARTITUDE-1 trial (NCT03548207) demonstrated that patients who received a single dose of ciltacabtagene autoleucel (cilta-cel; Carvykti) were alive and cancer-free 5 years after therapy, without the need for maintenance therapy.

Jagannath is a professor of Medicine specializing in hematology and medical oncology at the Icahn School of Medicine at Mount Sinai and The Tisch Cancer Institute.

What was the rationale for your talk on defining a cure in multiple myeloma?

It is important to change the dialogue in multiple myeloma. “Is it time to talk about cure in multiple myeloma?” This is an important topic for me. Why is it so important? Let’s put it in perspective. First, for the patient to be told that this is a curable cancer is completely different, as opposed to being told that they are afflicted with an incurable, invariably fatal cancer—it makes a big difference [in terms] of giving hope to the patient. Secondly, for the treating physician, it is important that they understand that, at this time, [multiple] myeloma is a curable cancer, which means they are engaging in patient care in a different way. They are keeping themselves up to date on the latest treatment. They are referring the patients for clinical trials with the potential for a cure. That makes a difference in how the physicians approach the patient.

Then, for the [pharmaceutical] industry, this is also important because if we have a definition for cure, and if it’s a definition that could have a time frame of 5 years, then the [pharmaceutical company] is engaged in developing new treatment plans with a 5-year goal of a potentially curative treatment. They are all engaged, so new clinical trials could be developed in newly diagnosed multiple myeloma with [developing] a cure as the goal. It also allows multiple pharmaceutical industry partners to work with each other, because once you say this is a potentially curative treatment protocol, they would like that asset to be part of the design of the trial. The pharmaceutical industry is very much engaged.

Finally, for the FDA and the EMA as regulatory [agencies], it is also important that there is an evidence-based end point whereby they could approve the drugs earlier as first-line therapy, so clinical trials can happen. Newly developed drugs could come in clinical trials, and in second-line and third-line [therapy], in a randomized fashion. There are a lot of benefits to that.

How was your presentation designed?

There was a presentation this year at [the American Society of Clinical Oncology (ASCO) Annual Meeting] and [the European Hematologic Association [EHA] Annual Congress], as well as a publication in the Journal of Clinical Oncology on the results of cilta-cel in a phase 1b/2 trial. Results were from 2018 and 2019, with the 5-year readout. What was amazing is that these patients, when they participated in the clinical trial, had traditionally relapsed/refractory multiple myeloma. At that time, they were an unmet medical need—that means either you participate in the clinical trial or you are looking at hospice. What was surprising was that 97 patients participated in the clinical trial, and after a median follow-up of [approximately] 5 years or 61 months, [about] one-third of the patients, or 32 patients, were alive and progression-free. Twelve of these patients who participated in the trial were studied every year for minimal residual disease [MRD] with bone marrow blood tests and PET/CT annually, and they were found to be cancer-free year after year for 5 years. That is the definition of a cure without any maintenance.

We [finally] have a treatment modality on a clinical trial, with multiple institutions participating and accelerated approval given by the FDA, where the long-term results show that one-third of the patients were alive and progression-free in a relapsed/refractory situation. That means potentially curing patients in the end stage. If you offer such treatment options earlier in the disease course, then you will get better results, and there have been clinical trials to support that.

Then we also looked at the results, which have been published. We had reported our results of studying patients with annual bone marrow for MRD blood test and PET/CT done. We found that patients who are [complete remission] MRD-negative, and PET/CT negative year after year for 5 years do not have to be maintained. Thereafter, they are cured. We found that not only half of the patients had newly diagnosed multiple myeloma, but almost 40% of the patients were in second [or] subsequent relapse, clearly proving that the cure definition we established holds true, not only for [patients with] newly diagnosed myeloma, but even in relapsed situations.

What was the biggest takeaway from your presentation?

Now that we have a definition for a cure, why is it so important at this time? [It’s] because [patients with] newly diagnosed multiple myeloma are receiving quadruplet therapy, both in transplant-eligible [populations] with transplant and in transplant-ineligible [populations]. The results are showing that, even at 2 years, many of the patients are able to achieve complete remission MRD negativity. If you [conduct] a 2-year landmark analysis of the patients who are MRD-negative at the 2-year mark, 80% are all still progression-free. These studies are ongoing, and we would be able to do annual MRD testing. We will be able to define how many years they have to be MRD negative to reach a plateau. We are finally seeing plateaus in multiple myeloma, and that is why it is important that we define a cure and talk about that we are curing patients with multiple myeloma, to move the field forward.

What would the clinical implications of defining a cure be?

For [patients with] newly diagnosed multiple myeloma at this time, and even in [patients with] relapsed multiple myeloma—you have to remember that continuous therapy is the goal. In the [phase 3 DETERMINATION trial (NCT01208662)], they showed continuous relevant maintenance made a big difference compared with the [phase 3 IFM study (NCT01191060)].^{2, 3} Patients are on continuous therapy.

What this cure definition does is that [it makes it so] they could have a finite number of treatments—5 years—and then you will be able to stop with the confidence that they are not going to relapse. At the most, there will be 1 or 2 relapses here and there. Over 90% of the patients are going to be cured. Number 2 is that patients who are newly diagnosed, when they see the doctor and are embarking on treatment, [will be told] that they could be potentially cured. Either I am going to cure you on the front line with a quadruplet therapy without transplant, or should you relapse, the immunotherapy, with CAR T and bispecific [antibodies] will also cure you. The third thing is that clinical trials incorporating the CAR T and bispecific or trispecific antibodies are ongoing. The physicians are now empowered to refer the patient to clinical trials, which have the potential for cure, because the complete remission MRD-negativity in these clinical trials is going to be [quite] high—70% to 80%. It is an important advancement in the field of multiple myeloma.

What presentations at the SOHO 2025 Annual Meeting are you most looking forward to seeing?

There will be lot of information [regarding] CAR T-cell therapy, and bispecific and trispecific [antibodies]. There is an oral presentation on trispecific antibody results without having to use CAR T-cell therapy [which are amazing], with less toxicity and almost equivalent outcomes. We need long term follow-up, but results of deep complete responses are impressive. Right now, following the immunological treatment with bispecific and trispecific antibodies, as well as different CAR T-cell results are exciting.

At the same time, there’s also progress in the traditional immunomodulatory drug therapy, or what we call CELMoDs. Hopefully, they will get approved. They are having dramatic results, and they have the capacity to [improve] the outcome of patients who have gone through CAR T or bispecific antibodies. Also, we are anxious to make sure that CELMoDs get approved in the near future for the treatment of multiple myeloma.

References

1. Jagannath S, Martin TG, Lin Y, et al. Long-term (≥5-Year) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2025;43(25):2766-2771. doi:10.1200/JCO-25-00760
2. Richardson PG, Jacobus SJ, Weller EA, et al. Triplet therapy, transplantation, and maintenance until progression in myeloma. N Engl J Med. 2022;387(2):132-147. doi:10.1056/NEJMoa2204925
3. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376(14):1311-1320. doi:10.1056/NEJMoa1611750