Centering discussion on a patient case of transplant-eligible newly diagnosed multiple myeloma, expert panelists consider optimal workup and management strategies.
Beth Faiman, PhD, MSN, APN-BC: Welcome to this Cancer Network® Around the Practice® program titled “Recent Advances in Multiple Myeloma: Insights From Experts at the Cleveland Clinic.” I’m your host, Beth Fairman. I’m a nurse practitioner at the Cleveland Clinic in Cleveland, Ohio, in the department of hematology and medical oncology. I have a great panel of experts joining me. I’d like to invite my esteemed colleagues to introduce themselves. Dr Mazzoni?
Sandra Mazzoni, DO: I’m Dr Sandy Mazzoni, and I’m also at the Cleveland Clinic in the department of hematology and oncology.
Jack Khouri, MD: Hi, I’m Jack Khouri. I’m a physician in the myeloma program at the Cleveland Clinic.
Beth Faiman, PhD, MSN, APN-BC: Dr Williams?
Louis Williams, MD: I’m Louis Williams. I’m also a physician in the myeloma department at the Cleveland Clinic.
Beth Faiman, PhD, MSN, APN-BC: Thank you, and thanks for joining me. We’re going to discuss several key data updates in multiple myeloma treatment landscape from various studies. We’ll review these data in the context of 3 clinical cases and discuss how we can apply recent evidence to our clinical practice to improve patient outcomes.
Before we get started with our first case, I’d like to turn to Dr Mazzoni. Please tell us your general approach to treatment of myeloma. Do you use 2 drugs, 3 drugs, or 4 drugs? What are your thoughts?
Sandra Mazzoni, MD: It depends on the patient—what other comorbidities they have, what their age is, and more important, is the patient going to be transplant eligible? That’s my big determination withpatients: transplant eligibility, and having that discussion with them up front about what regimen is going to be best suited for them. There are always multiple options, so it’s case by case.
Beth Faiman, PhD, MSN, APN-BC: And clinical trials, right? Are they super important?
Sandra Mazzoni, DO: Also very important, yes.
Beth Faiman, PhD, MSN, APN-BC: Let’s dive in to our first patient case. This is a 54-year-old who had worsening fatigue and activity intolerance and presented to their primary care provider. Unfortunately, when labs were obtained, you saw a hemoglobin of 10.2 g/dL. No other cytopenias were present, but the CMP [comprehensive metabolic panel] showed hypercalcemia with a calcium of 14.7 mg/dL; serum creatinine was 5.25 mg/dL. Immediately, that individual was sent to the emergency department. Subsequently, a urinalysis was performed, and it showed an elevated random protein with a beta-globulin level of 78%. After that, the astute practitioner obtained serum free light chains in addition to SPEP [serum protein electrophoresis] and UPEP [urine protein electrophoresis]. The SPEP showed no M-spike [monoclonal protein] as we would expect with a lambda free serum; that’s pretty high. Additionally, he had suffered with some back pain. Lumbar x-rays showed some vertebral compression fractures and osteolytic lesions, and the PET [positron emission tomography] scan showed widespread disease. He was admitted to the hospital, and a bone marrow aspirate and biopsy were performed, showing a lambda monotypic plasma cell population with about 50%. Congo red stain was negative for amyloidosis. At the time, we didn’t know it—we’ll talk about cytogenetics in a moment—but unfortunately he had aberrant cytogenetics and had a gait of 1q, deletion of 13, 14, 17p as well as translocation 414. This individual had high-risk disease. What are your thoughts, Dr Khouri, on this type of individual? How would you think about initial management of this patient with renal failure, hypercalcemia and these types of characteristics?
Jack Khouri, MD: The patient’s presentation is clearly very aggressive. He’s got triple-hit disease with 3 high-risk cytogenetic abnormalities with kidney failure, which is also a problem that we see frequently. I’d start with fluids to help the hypercalcemia. At our center, we consider plasma exchange for cast nephropathy to drop the light chains quickly. If he needs dialysis, obviously dialysis would be recommended, and then I’d start with induction therapy right away in the hospital. We typically consider bortezomib. We favor biweekly bortezomib with steroids and dexamethasone, and we add cyclophosphamide.
Beth Faiman, PhD, MSN, APN-BC: Absolutely. He was started on treatment with bortezomib, and interestingly the clinician recommended lenalidomide and dexamethasone. You had mentioned cyclophosphamide. Dr Williams, would you recommend bortezomib-lenalidomide-dexamethasone for this patient on dialysis with these cytogenetic findings?
Louis Williams, MD: It’s difficult to do well in the hospital. You can give lenalidomide to patients who are on dialysis, even in the cases of kidney injury. I don’t like to do it while the kidney function is fluctuating and potentially changing. At diagnosis, I don’t use lenalidomide in cases like these. I favor cyclophosphamide. We typically transition to lenalidomide afterward, once renal function is stable.
Beth Faiman, PhD, MSN, APN-BC: Exactly. With these types of drugs we’d consider shingles prevention with dose-adjusted acyclovir, according to the renal failure. We talked about denosumab, which might be more reasonable after discharge from the hospital based on his renal function. We’ll talk about VTE [venous thromboembolism] prophylaxis in a few moments. After this patient’s discharge, we found out the genetics. They were started on VRd [bortezomib, lenalidomide, dexamethasone] in the hospital. Based on the high-risk genetics—would you call it quadruple-hit myeloma?—it’s a lot. I added subcutaneous daratumumab hyaluronidase, and it had an impressive response. It went from 15,143 light chains to 45.3. That’s important. At what point would you check MRD [minimal residual disease] status? Let’s say he went through 3 cycles of therapy. Would you look at bone marrow evaluation and look for MRD-negative status? Would you consider him a transplant candidate at any point? Who wants to chime in with high-risk disease?
Louis Williams, MD: I can chime in there. I’d eventually like to know MRD status, but we don’t check until we reach at least a VGPR [very good partial response]. It’s important to remember that the serum proteins that we monitor are lagging indicators of disease status, so they tend to normalize after you’ve gotten rid of the plasma cells. This early on in treatment, I probably wouldn’t be looking for MRD, but eventually it plays a role.
Transcript edited for clarity.