This month, Joseph Mikhael, MD, MEd, discusses approaches for a fit 72-year-old patient with very active myeloma.
And don’t forget to check out next month’s clinical dilemma – send in your responses for a chance to win an ASH Clinical News-themed prize!
In Norway, I follow a fit 72-year-old patient who was diagnosed with IgG-lambda myeloma in the summer of 2016. At that time, he had anemia, osteolytic lesions, and renal dysfunction. He was treated with lenalidomide plus dexamethasone, but this gave him even more renal dysfunction with no response. After that, he was treated with daratumumab, bortezomib, and dexamethasone (we don’t have daratumumab plus pomalidomide and dexamethasone), but there was no effect. Pomalidomide plus low-dose dexamethasone was effective, as was daratumumab plus pomalidomide and dexamethasone. Now he has a bulky plasmacytoma in his thorax, which was treated with radiation but with bad results.
He is fit, but he is 72 years old and has a very active disease. What would you advise? Back to some traditional chemotherapy to see whether he tolerates it? Melphalan, but in combination with what?
This is a challenging case of relapsed myeloma that falls into the category of “triple-class refractory” disease. We give this designation to patients whose condition has progressed despite treatment with proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. With the greater use of these agents, especially in combination and with next-generation forms of these drugs, this heavily pretreated myeloma can be very difficult to control.
My approach to this involves the following strategies:
- Optimizing all agents in the three classes. As in this case, there may be certain drugs in these classes that have not been used or to which the patient may not be truly refractory. We also know the disease can clonally evolve and there may be sensitivity to previously used agents. This may justify reusing prior agents also.
- Use of conventional chemotherapeutic agents. Especially in situations like this case with a high burden of disease, regimens such as DPACE (dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide) may be able to debulk the disease to bridge to another therapy.
- Selinexor was just approved by the U.S. Food and Drug Administration for patients who have had four or more prior lines of therapy including two proteasome inhibitors, two immunomodulatory drugs, and a monoclonal antibody.
- There are a host of clinical trials for patients with advanced myeloma that, if available, can be excellent options. These include novel antibodies, bispecific therapies, cell-modifying agents, and chimeric antigen receptor (CAR) T-cell therapy against B-cell maturation antigen (BCMA) and other targets.
This case also highlights the critical importance of open and honest discussion with the patient regarding the severity of the condition, the need for supportive care, and, perhaps most important, the patient’s own preferences.
- Mikhael, J. Treatment options for triple-class refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2019 September 29. [Epub ahead of print]. www.sciencedirect.com/science/article/pii/S2152265019320087
- Gerrie AS, Mikhael JR, Cheng L, el al. D(T)PACE as salvage therapy for aggressive or refractory multiple myeloma. Br J Haematol. 2013;161:802-10.
- Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381:727-38.
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NEXT MONTH'S CLINICAL DILEMMA
I have an 85-year-old male patient with a history of ulcerative colitis on disease-modifying antirheumatic drug therapy who presented with an iliofemoral deep vein thrombosis (DVT) with phlegmasia cerulea dolens. He required urgent catheter-directed thrombolysis with a venous stent placement and is on full-dose oral apixaban 5 mg twice daily, with baby aspirin. He was not immobile preceding the DVT, and his only risk factor appears to be the inflammatory disease. He has normal renal and hepatic function. I was considering changing him to lower-dose of apixaban 2.5 mg twice daily now that he is stable. I realize the AMPLIFY-EXT trial was open only to patients who had less severe presentations and there was equipoise between continuing versus stopping anticoagulation. Can we extrapolate those results to this setting where likely indefinite anticoagulation is indicated?
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