Andrzej Jakubowiak, MD, PhD, director, Myeloma Program, University of Chicago Medicine, discusses initial efficacy results from the phase 3 ATLAS trial (NCT02659293) in multiple myeloma.

The phase 3 ATLAS trial compared maintenance therapy with lenalidomide (Revlimid) carfilzomib (Kyprolis) and dexamethasone (KRd) with standard-of-care (SOC) lenalidomide alone in patients with newly diagnosed multiple myeloma who completed autologous stem cell transplant (ASCT) after induction therapy.

The study’s primary end point was progression-free survival (PFS), while secondary endpoints included rate of minimal residual disease (MRD) at 6, 12, 18, 24, and 36 months post-randomization, correlation of MRD with PFS, duration of MRD, depth of esponse, improvement in the depth of response at 6 and 12 months, overall survival (OS), and safety, Jakubowiak begins. Statistical modelling for the ATLAS trial was based on historical data from the CALGB-100104 trial NCT00114101) and the phase 2 FORTE trial (NCT02203643

zAn unplanned interim analysis of the trial occurred after 61% of the 96 expected events occurred at a median follow-up of 33.8 months. Initial findings showed that maintenance KRd significantly improved median PFS vs lenalidomide monotherapy but did not affect OS in this population, Jakubowiak continues. Additionally, MRD negativity correlated with increased PFS in the KRd arm. Notably, this difference in PFS met the threshold required to demonstrate statistical significance, Jakubowiak explains.

Final analysis is planned to confirm these findings. However, preliminary survival results signal that post-transplant KRd could be a viable alternative to the current SOC, Jakubowiak concludes. 

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Andrzej Jakubowiak, MD, PhD, discusses initial efficacy results from the phase 3 ATLAS trial in multiple myeloma.

Dr. Jakubowiak on Initial Efficacy Data From the ATLAS Trial in Multiple Myeloma

Andrzej Jakubowiak, MD, PhD, professor of medicine, director, Myeloma Program, The University of Chicago Medicine, discusses a phase I study of daratumumab (Darzalex) in combination with carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) in patients with newly diagnosed multiple myeloma.

Investigators believe progress is being made with some other novel regimens in multiple myeloma and able to get several patients to minimal residual disease (MRD)-negativity, Jakubowiak says. KRd, as a triplet, has emerged as an active regimen that has performed better against other therapies, he says. Additionally, KRd can be further improved by implementing transplant.

Rather than transplant, researchers sought to combine KRd with daratumumab, defined by Jakubowiak as one of the most promising agents in the field. Thus far, regimens explored with daratumumab have shown great promise, leading to the rationale for this study.

Dr. Jakubowiak on Phase I Daratumumab Regimens in Newly Diagnosed Multiple Myeloma

Andrzej Jakubowiak, MD, PhD, professor of Medicine, director, Myeloma Program, University of Chicago Medicine, discusses minimal residual disease (MRD) in multiple myeloma.

The combination of the proteasome inhibitor carfilzomib (Kyprolis) with lenalidomide (Revlimid) and dexamethasone demonstrated significant efficacy in a phase I and II studies in relapsed multiple myeloma.

Disease assessments were made with the use of the International Myeloma Working Group Uniform Response Criteria, with minimal response defined according to European Society for Blood and Marrow Transplantation criteria.

Andrzej Jakubowiak, MD, PhD, professor of Medicine, director, Myeloma Program, University of Chicago Medicine, discusses minimal residual disease in multiple myeloma.

Dr. Jakubowiak on Minimal Residual Disease in Multiple Myeloma

Andrzej Jakubowiak, MD, PhD, professor of Medicine, director, Myeloma Program, University of Chicago Medicine, discusses the options for finding a cure for patients with multiple myeloma.

Enough disease is being eliminated in patients with myeloma that researchers can begin identifying patients who are in indefinite or extended remissions, Jakubowiak explains. Because of this, it would be helpful to incorporate tools such as MM Profiler, which can determine if patients are at standard or high risk, into clinical practice. 

The goal of finding a cure for multiple myeloma should not be lost, Jakubowiak says. However, he adds that researchers should also identify the patients that do not require overtreatment.

Andrzej Jakubowiak, MD, PhD, professor of Medicine, director, Myeloma Program, University of Chicago Medicine, discusses the likelihood of finding a cure for patients with multiple myeloma.

Dr. Jakubowiak on Finding a Cure for Patients With Multiple Myeloma

Andrzej Jakubowiak, MD, PhD, professor of medicine, director, Myeloma Program, University of Chicago Medicine, discusses the impact of autologous stem cell transplant (ASCT) with kyprolis/revlimid/dexamethasone (KRd) for patients with newly diagnosed multiple myeloma.

In a phase II trial, patients were randomized to either receive KRd plus ASCT or KRd alone. Patients in the combination group received four 28-day cycles of induction therapy followed by stem cell collection (SCC), melphalan and ASCT, and then KRd consolidation. Patients then went on to receive KRd maintenance.

 After KRD consolidation stringent complete response (sCR ) rates were 72% for KRd+ASCT group (n=50) compared to 30% for KRd-alone group (n=44). After maintenance therapy sCR rates were 88% (n=26) in the combination group versus 51% (n=41) in the KRd-alone group.

These data show that ASCT is still valid even with effective regimens like KRd available, says Jakubowiak.

The phase II study was an update to any earlier phase 1/2 trial looking at the same combination versus KRd alone. At 4-year follow-up of that study progression-free survival was 69% for patients treated with KRd+ ASCT. These results are some of the best seen in newly diangoised multiple myeloma, says Jakubowiak.

Dr. Jakubowiak on Improved Efficacy with ASCT+ KRd in Multiple Myeloma

Andrzej Jakubowiak, MD, PhD, professor of medicine, director, Myeloma Program, University of Chicago Medicine, discusses the current and future state of multiple myeloma treatment.

Over the last 10 years, multiple myeloma has made one of the most impressive advances in treatment with prolongations of remissions and life. Recent research has shown a threefold increase of life expectancy compared to 10 years ago, Jakubowiak says.

Jakubowiak says in the last 10 years, 2 proteasome inhibitors and 3 immunomodulatory drugs have been approved. These drugs can be combined in order to elicit great responses and great improvements in progression-free survivals. However, physicians may not be able to make more improvements with these current drugs.

Now, researchers are looking into a group of antibodies that may help enhance the ability to treat the disease and increase to life expectancy of patients with myeloma.

Andrzej Jakubowiak, MD, PhD, professor of medicine, director, Myeloma Program, University of Chicago Medicine, discusses the current and future state of multiple myeloma treatmen

Dr. Jakubowiak Discusses the Future of Multiple Myeloma Treatment

Andrzej Jakubowiak, MD, PhD, professor of medicine, director, Myeloma Program, University of Chicago Medicine, discusses the toxicity profile of panobinostat in combination with bortezomib and dexamethasone in relapsed or relapsed/refractory multiple myeloma as seen in the PANORAMA trial.

Jakubowiak says ideally, researchers aim to create a drug or drug combination that is more active with less toxicity. In the PANORAMA trial, there was a higher proportion of GI toxicities in the panobinistat arm compared to the placebo arm. There was also a higher rate of thrombocytopenia and other hematological toxicities. However, all of the toxicities were mostly manageable and did not impact the outcome, Jakubowiak says.

More details are needed to get a better understanding of the toxicity profile of this combination in this setting, Jakubowiak says.

Andrzej Jakubowiak, MD, PhD

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