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ASH 2018: Dr. Landgren Highlights Pivotal Myeloma Data

C. Ola Landgren, MD, PhD
Published: Friday, Jan 11, 2019



C. Ola Landgren, MD, PhD, chief, Myeloma Service, Memorial Sloan Kettering Cancer Center, highlights the pivotal data in the field of multiple myeloma that were presented at the 2018 ASH Annual Meeting.

Findings from the phase III MAIA study showed that the frontline triplet of daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone (DRd) reduced the risk of disease progression or death by 44% compared with lenalidomide plus dexamethasone (Rd) in newly diagnosed patients with multiple myeloma who were not candidates for high-dose chemotherapy and transplant.

At a median follow-up of 28 months (range, 0.0-41.4), the median progression-free survival (PFS) had not been reached with DRd compared with 31.9 months in the Rd group (HR, 0.56; 95% CI, 0.43-0.73; P <.0001). The PFS rate at 30 months was 71% versus 56%, respectively. Landgren says this study has the potential to introduce a new standard of care for these patients.

Moreover, results from part 2 of the phase IIb STORM study, which is evaluating the use of selinexor in combination with low-dose dexamethasone in penta-refractory myeloma patients, showed a median PFS of 3.7 months and a median overall survival of 8.0 months with the combination. Landgren stresses that this population consisted of heavily pretreated patients who have failed all other FDA-approved combinations. Due to the gastrointestinal toxicities that have been observed with selinexor—such as diarrhea, nausea, fatigue, and asthenia—more work still needs to be done, he explains.

There were also studies looking at the optimal triplet regimen for relapsed/refractory patients. Although the regimen comprised of lenalidomide, dexamethasone, and bortezomib (Velcade) is probably most commonly used in private practice, the triplet consisting of carfilzomib, dexamethasone, and lenalidomide (KRd) has more uptake in academic centers, according to Landgren, who says he uses the latter in his practice, as he feels it is a more potent regimen.

Four-drug regimens are also starting to make headway in this setting. Updated data from the Griffin trial, which evaluated the quadruplet regimen of daratumumab, bortezomid, lenalidomide, and dexamethasone, showed that the addition of daratumumab results in deeper responses and better PFS. Landgren emphasizes that the data are very early, and the trial has not yet read out its primary endpoint.

Data from a correlative and clinical phase II trial evaluating the addition of daratumumab to KRd was also read out at the meeting. Using parallel bone marrow-based and blood-based minimal residual disease (MRD) testing along with targeted DNA sequencing of baseline bone marrow samples, Landgren and his team showed up to 80% of MRD negativity with the regimen in patients with newly diagnosed myeloma; this is without transplant. Although Landgren admits these are still early data looking at a small number of patients, it is still very promising. He feels that 4-drug regimens will eventually become the new standard of care for patients who are fit enough.

Results from the phase III TOURMALINE–MM3 trial evaluating maintenance therapy with ixazomib (Ninlaro) in patients with newly diagnosed myeloma after transplant, showed that the addition of the oral proteasome inhibitor significantly prolonged PFS by about 4 months compared with placebo. The PFS benefit is still less than what had been observed with the addition of lenalidomide, so ixazomib will probably not be able to replace lenalidomide, adds Landgren. However, for the patients who go on lenalidomide maintenance who are unable to tolerate it, this offers another option.
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C. Ola Landgren, MD, PhD, chief, Myeloma Service, Memorial Sloan Kettering Cancer Center, highlights the pivotal data in the field of multiple myeloma that were presented at the 2018 ASH Annual Meeting.

Findings from the phase III MAIA study showed that the frontline triplet of daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone (DRd) reduced the risk of disease progression or death by 44% compared with lenalidomide plus dexamethasone (Rd) in newly diagnosed patients with multiple myeloma who were not candidates for high-dose chemotherapy and transplant.

At a median follow-up of 28 months (range, 0.0-41.4), the median progression-free survival (PFS) had not been reached with DRd compared with 31.9 months in the Rd group (HR, 0.56; 95% CI, 0.43-0.73; P <.0001). The PFS rate at 30 months was 71% versus 56%, respectively. Landgren says this study has the potential to introduce a new standard of care for these patients.

Moreover, results from part 2 of the phase IIb STORM study, which is evaluating the use of selinexor in combination with low-dose dexamethasone in penta-refractory myeloma patients, showed a median PFS of 3.7 months and a median overall survival of 8.0 months with the combination. Landgren stresses that this population consisted of heavily pretreated patients who have failed all other FDA-approved combinations. Due to the gastrointestinal toxicities that have been observed with selinexor—such as diarrhea, nausea, fatigue, and asthenia—more work still needs to be done, he explains.

There were also studies looking at the optimal triplet regimen for relapsed/refractory patients. Although the regimen comprised of lenalidomide, dexamethasone, and bortezomib (Velcade) is probably most commonly used in private practice, the triplet consisting of carfilzomib, dexamethasone, and lenalidomide (KRd) has more uptake in academic centers, according to Landgren, who says he uses the latter in his practice, as he feels it is a more potent regimen.

Four-drug regimens are also starting to make headway in this setting. Updated data from the Griffin trial, which evaluated the quadruplet regimen of daratumumab, bortezomid, lenalidomide, and dexamethasone, showed that the addition of daratumumab results in deeper responses and better PFS. Landgren emphasizes that the data are very early, and the trial has not yet read out its primary endpoint.

Data from a correlative and clinical phase II trial evaluating the addition of daratumumab to KRd was also read out at the meeting. Using parallel bone marrow-based and blood-based minimal residual disease (MRD) testing along with targeted DNA sequencing of baseline bone marrow samples, Landgren and his team showed up to 80% of MRD negativity with the regimen in patients with newly diagnosed myeloma; this is without transplant. Although Landgren admits these are still early data looking at a small number of patients, it is still very promising. He feels that 4-drug regimens will eventually become the new standard of care for patients who are fit enough.

Results from the phase III TOURMALINE–MM3 trial evaluating maintenance therapy with ixazomib (Ninlaro) in patients with newly diagnosed myeloma after transplant, showed that the addition of the oral proteasome inhibitor significantly prolonged PFS by about 4 months compared with placebo. The PFS benefit is still less than what had been observed with the addition of lenalidomide, so ixazomib will probably not be able to replace lenalidomide, adds Landgren. However, for the patients who go on lenalidomide maintenance who are unable to tolerate it, this offers another option.
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