Patient Case 1: Transplant-Eligible Newly Diagnosed Multiple Myeloma
Expert panelists review the case of transplant-eligible newly diagnosed multiple myeloma and consider optimal selection of induction therapy.
Transcript:
Alfred Garfall, MD:Welcome to this CancerNetwork® Around the Practice program titled “Recent Advances in Multiple Myeloma: Insights From Experts at the University in Pennsylvania.” I’m your host, Dr Alfred Garfall, and I’m an assistant professor of medicine at the Hospital of the University of Pennsylvania [in Philadelphia]. I have a great panel of experts who have joined me today. I would like to invite my esteemed fellow panelists to introduce themselves.
Edward Stadtmauer, MD: Hi, I’m Ed Stadtmauer. I’m a professor of medicine in the myeloma program at the University of Pennsylvania.
Dan Vogl, MD: Hi, I’m Dan Vogl. I’m also in the myeloma program at the University of Pennsylvania. I’m an assistant professor of medicine.
Sandra Susanibar-Adaniya, MD:Hi, I’m Dr Sandra Susanibar-Adaniya. I’m also part of the myeloma program. I’m an assistant professor at the University of Pennsylvania.
Alfred Garfall, MD:Thank you all for joining me. We’re going to discuss 3 clinical cases of patients with multiple myeloma, who we’ve treated at the University of Pennsylvania, and our approach to their treatment in the context of the available evidence. We’ll also review key data updates from recent meetings, such as IMS [International Myeloma Society Annual Meeting and Exposition], EHA [European Hematology Association Congress], and ASCO [American Society of Clinical Oncology Annual Meeting] in 2022, and discuss how we can apply the data to our clinical practice to improve patient outcomes. Let’s begin.
Our first case is a 60-year-old man who presented with back pain and shortness of breath. The patient underwent an MRI of the spine that showed an enhancing, expansile lesion involving S1 and S2 and a diffusely abnormal bone marrow signal. The initial laboratory evaluation showed a white blood cell count of 3.1 per mm3, a hemoglobin count of 6.3 g/dL, platelets at 380 per mm3, a creatinine count of 6.37 mg/dL, a calcium level of 9.4 mg/dL, albumin at 4.6 g/dL, a very elevated serum free kappa light chain of 43,109 mg/L, an elevated beta-2 microglobulin level of 13.1 mg/L, and an elevated LDH [lactate dehydrogenase] of 495 U/L. The patient underwent a bone marrow biopsy that yielded a limited sample, but it did demonstrate a kappa-restricted plasma cell neoplasm. FISH [fluorescence in situ hybridization] study showed deletion of 17p.
The patient started therapy in the hospital with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. He continued this as an outpatient to complete 2 cycles, at which point the patient’s kidney function stabilized with a creatinine of 2.5 mg/dL. At that point, the patient was transitioned to daratumumab, bortezomib, lenalidomide, and dexamethasone and continued therapy from there.
The patient’s serum-free light chain ratio normalized very nicely after the initial treatment with dara-CyBorD [daratumumab, cyclophosphamide, bortezomib, dexamethasone]. The patient completed 4 additional cycles with daratumumab–VRd [bortezomib, lenalidomide, dexamethasone] and then proceeded to consolidate the response with high-dose melphalan reduced to 140 mg/m2 because of the residual renal insufficiency and autologous stem cell transplant. The patient subsequently enrolled in a clinical trial after recovery from transplant, the SWOG S1803 study, which evaluated lenalidomide vs daratumumab and lenalidomide as maintenance therapy after transplant. It was randomized to the daratumumab arm. He continues on maintenance therapy with daratumumab and lenalidomide. I thought we would discuss a little how this patient was treated. Dr Vogl, could you talk about the rationale for choosing the treatment regimen that the patient received?
Dan Vogl, MD: First, it’s important to realize that this patient had a very high tumor burden, with high myeloma staging and poor prognostic features, as well as acute renal failure. They needed a treatment regimen that would induce a rapid and deep response to improve organ function quickly. In the setting of renal insufficiency, we tend to avoid starting patients with a lenalidomide-based regimen because lenalidomide is renally cleared. Therefore, it can be difficult to pick the right dose when patients present with renal function that may be changing rapidly over the initial month or 2 of therapy.
The standard approach for the patient who presents in renal function really should be the combination that he got, which is daratumumab with cyclophosphamide, bortezomib, and dexamethasone. These agents all have the advantage that they are not renally cleared, and they can be given safely at full dose to a patient regardless of their renal function. Although in the past we didn’t necessarily include daratumumab, daratumumab is so effective and adds so little toxicity that it makes sense to include for a patient like this, as part of their initial therapy, to induce that rapid, deep response. Once the renal function improves, it makes sense to switch to the combination that has the best data for an initial therapy of myeloma, which is a lenalidomide-bortezomib combination. That’s what this patient got, and then he switched to daratumumab, lenalidomide, bortezomib, and dexamethasone.
Transcript edited for clarity.
