A 75-Year-Old Woman With Multiple Myeloma - Episode 4

The MAIA & PEGASUS Trial and Managing Patients Receiving DRd

The MAIA & PEGASUS Trial and Managing Patients Receiving DRd

Saad Usmani, MD: More recently there was a study called PEGASUS that did an indirect comparison between the DRd [daratumumab, lenalidomide, dexamethasone] patients treated on the MAIA trial and the common standard-of-care regimens utilizing the Flatiron Health electronic medical record database. Patient data would be identified, and there were individual patient data.

These data were used to perform what is called an indirect treatment comparison, or an anchor treatment indirect comparison, with DRd [daratumumab, lenalidomide, dexamethasone]. The comparison was with VRd [bortezomib, lenalidomide, dexamethasone], Vd [bortezomib, dexamethasone], and Rd [lenalidomide, dexamethasone].

This is not a randomized up-front clinical trial. This is an indirect comparison. We have to take these results with a grain of salt. But in the absence of a direct-comparison clinical trial of DRd [daratumumab, lenalidomide, dexamethasone] vs VRd [bortezomib, lenalidomide, dexamethasone], these are probably the best data for now.

It was encouraging to see that, when compared with the identified data sets for those patients, DRd [daratumumab, lenalidomide, dexamethasone] was associated with a lower risk of progression on depth compared with VRd [bortezomib, lenalidomide, dexamethasone]. And in the absence of a head-to-head trial comparison, these data tell us if you’re picking DRd [daratumumab, lenalidomide, dexamethasone] over VRd [bortezomib, lenalidomide, dexamethasone] for whatever reason in transplant-ineligible patients, it’s reasonable to do that.

We’re never going to—at least not in the immediate future—have a triplet-vs-triplet trial in the setting. But these may be the best data that we get.

Looking at DRd [daratumumab, lenalidomide, dexamethasone] as an option for our given patient, it will not give you the same kind of neuropathy as you would get with VRd [bortezomib, lenalidomide, dexamethasone], especially in the patient with diabetes who already has early signs of neuropathy.

The important piece is the overall tolerability. If you look at the MAIA data, there were no safety signals that led to this continuation of a drug that was unique compared with the Rd [lenalidomide, dexamethasone]. There were higher incidents of infections in the DRd arm [daratumumab, lenalidomide, dexamethasone], as well as neutropenia. But they did not result in discontinuation of treatments.

One of the key things I want to highlight is that older patients in general have an immunosuppressive state. It’s more important in older patients to watch for infections and do appropriate dose modifications of Revlimid [lenalidomide] specifically.

This is something we have observed in the clinic: Most patients require dose adjustments of lenalidomide, or even in the relapsed setting pomalidomide, when they’re combined with daratumumab. Our general practice is to start with the low dose of Revlimid [lenalidomide] in older patients along with daratumumab. Based on tolerability and response, we see if we can move the dose up. We generally don’t start with a 25-mg dose in our clinical practice.

Those are some of the clinically relevant points for when managing patients receiving DRd [daratumumab, lenalidomide, dexamethasone].

Transcript edited for clarity.


Case: A 75-Year-Old Woman With Multiple Myeloma

Initial Presentation

  • An active 75-year-old woman presented with new onset back pain and a 10-month history of fatigue, mild sensory neuropathy
  • PMH: hypercholesterolemia, diabetes, and atrial fibrillation; all medically controlled
  • PE: bony tenderness appreciated on the hips and lower back


Clinical Workup

  • Labs: Hb 10.2 g/dL, calcium 11.1 mg/dL, LDH 186 U/L, creatinine 1.3 mg/dL, albumin 3.7 g/dL, beta-2 microgloblulin 3.6 mcg/mL, potassium 1100 g/dL, M-protein 2.6 g/dL, lambda free light chains 4.1 mg/dL
  • Hepatitis B and C negative
  • X-ray showed L4 vertebral compression fracture
  • Skeletal survey showed multiple lytic lesions in femur
  • Bone marrow shows 40% clonal plasma cells IgG k with hyperdiploidy FISH
  • Diagnosis: R-ISS stage II MM
  • ECOG 1

Treatment

  • Patient is ineligible for ASCT due to comorbidities
  • Initiated treatment with daratumumab + lenalidomide + dexamethasone