Clinical Trial Data in the Setting of TCR MM
Adriana Rossi, MD, describes key clinical trials and their implications for the management of triple-class refractory multiple myeloma.
Adriana Rossi, MD: The approval of belantamab comes following the study called DREAMM-2, which was a single-agent monotherapy with belantamab in 2 different drug levels. The cohorts were either receiving 2.5 or 3.4 mg/m2 on a schedule of once every 3 weeks. There were a total of nearly 200 patients enrolled, split evenly between the 2 arms. Overall response was the primary end point. In the 2.5 mg, which was the chosen dose, the overall response rate was 30%. And as far as toxicity, again, it was mostly hematologic, so thrombocytopenia, anemia, and leukopenia were all noted at about 20%. But the ocular toxicity is the one that got the most attention. It was the most frequent grade 3/4 toxicity, and it occurred in up to 27% of patients, requiring dose reductions, dose modifications, and rarely, discontinuation. Over about 50% of patients required dose delays, and these were significant, usually longer than another cycle. One cycle is 21 days, and there were a number of patients who required over 3 cycles of delays. Dose reductions were required in about one-third of the patients, but discontinuations were rare.
In addition to overall response rate, we do have a presentation of PRO [patient-reported outcome], which was a very important addition examining the quality of life of patients while on therapy. And fatigue and pain, which are very difficult and challenging things to treat, improved over time. Even in patients who did have significant ocular toxicity, they’re functional role and their ability to continue to do the things they wished to do were unhindered. It was interesting to see that even though this is a significant toxicity, and it does require mitigation and a game plan, it really does not seem to affect the patient’s quality of life negatively.
In addition to the excellent overall response that we see in these heavily pretreated patients, as far as the toxicity profile, we’re all comfortable and well aware of the hematologic toxicity, and all 3 lines have been affected. Thrombocytopenia is the most commonly seen grade 3/4 of the hematologic toxicities. But also, the keratopathy. Sometimes patients are asymptomatic and require an ocular examination to identify the cysts, which can aggravate their vision and potentially become difficult to reverse. One of the most important things is to partner with an ophthalmologist or optometrist, which I think is something we forget sometimes. Optometrists are perfectly able to do these exams and make sure that patients are being followed and have an ocular exam before each dose. This has absolutely facilitated. There is a lot of education for our ophthalmologic partners, and it’s important to have the patient sent up late in the cycle, just before the next dose, because our experience has been that many times it’s in that third week that the ocular toxicity will show up. Some patients will have vision changes, or a dry eye feeling. However, many of them will have no symptoms and really require the testing.
The important thing is to focus on the response. Even though the approved schedule is once every 3 weeks, this is how the original study was done, there was an interesting presentation at SOHO [Society of Hematologic Oncology annual meeting] 2020 that showed that patients who had up to a 3- cycle delay, so 63 days or greater, did not lose their response. So 88% of those patients were able to maintain their clinical benefit. About one-third of them actually deepened their response, with another third maintaining, and only 2 patients going on to progress and lose their response due to the delay. So, in ongoing clinical trials, there are now new schedules, dosing once every 4 weeks, or even wider, which may allow patients to stay on therapy and not require a change, and not be allowed to progress. Adjusting it to the patient’s needs and making sure the dosing is done safely is absolutely in their greatest benefit.
Transcript edited for clarity.
Case: A 75-Year-Old Woman with Triple-Class Refractory Multiple Myeloma
Initial Presentation
- A 75-year-old woman diagnosed with multiple myeloma 5 years ago returns to the clinic with complaints of extreme fatigue, increased muscle weakness and new bone pain in her right hip, right forearm and low back. She reports that she is currently taking antibiotics for a bacterial infection, her third in the last 12 months.
- Treatment history:
- Initially treated with DRd; CR lasting 20 months
- Switched to VRd, stable disease lasting 16 months
- Subsequently switched to KPd, achieved a PR lasting 12 months
- Started selinexor; follow up at 9 months showed M protein increase by 0.5 g/dl; patient continued to feel well
- Currently, 3 months after her last visit, she returns to the clinic for follow-up
- PE: new bony tenderness appreciated on right hip, pelvis forearm and lumbar spine; bruising and mild bleeding of the gums
Clinical Workup
- Labs: Hb 6.2 g/dL, calcium 8.4 mg/dL, LDH 160 U/L, creatinine 2.1 mg/dL, albumin 2.7 g/dL, b2 microgloblulin 4.9 mcg/mL, serum M-protein 4.2 g/dL, lambda free light chains 4.1 mg/dL
- HBV negative
- Skeletal survey and MRI revealed lytic bone lesions in the left hip, pelvis and L2 vertebrae and lytic lesions as well as a hairline fracture in the distal radius of the right arm
- Bone marrow shows 62% plasma cells IgG k
- FISH: t(11;14) at diagnosis; new del(17p)
- Diagnosis: R-ISS stage II MM
- ECOG 1
Treatment
- Initiated treatment with belantamab mafodotin
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