Oncology Case Challenge: A Daily Beer Drinker With Bruises, Back Pain, and Bleeding

Arun Gupta, MD, DNB

Disclosures

July 28, 2022

Due to the absence of high serum immunoglobulin levels in NSMM, the rouleaux formation and high ESR may not be observed. An elevated level of alkaline phosphatase and LDH enzymes may be found, the latter being predictive of an aggressive clinical course. Beta-2 microglobulin levels may also be elevated and tend to directly correlate with tumor burden. Bone marrow biopsy shows infiltration by plasma cells in the range of 20%-90%.

Once diagnosed, disease staging is accomplished with the traditional Durie-Salmon staging system or the now more commonly used International Staging System (ISS). ISS defines factors that influence a patient's survival and has 3 stages that are based on the levels of serum albumin and beta-2 microglobulin. The overall median survival is 62 months for stage I, 44 months for stage II, and 29 months for stage III disease. Other factors that influence the prognosis and survival are the status of a patient's renal function, plasma cell morphology, plasma cell labeling index (PCLI), and chromosomal changes.[9,10,11]

The PCLI may be helpful in establishing a diagnosis of myeloma and can provide information about the prognosis. The PLCI provides a measure of the proliferative rate of the malignant bone marrow plasma cells.[12] A PCLI of ≥ 1% is a strong indicator of active disease and indicates a worse prognosis.

Serum free light chain (sFLC) testing is another potential tool to determine multiple myeloma disease progression and treatment response. Khoriaty et al evaluated the use of sFLC in assessing patients with nonsecretory multiple myeloma, as proposed by the International Myeloma Working Group (IMWG) response and progression criteria.[13] Although the investigators corroborated the prognostic reliability of sFLC testing, this assay was limited by the fact that half of the patients' disease was not evaluable (as defined by sFLC <100 mg/L). Thus, the sFLC assay can be used to monitor the course of multiple myeloma and the effect of therapy only in patients whose sFLC is measurable (100 mg/L or greater).[13] Further investigation is needed.

The main goal when treating myeloma is to control the disease and to provide comfort for patients. Different treatment modalities are available including chemotherapy, radiation therapy, immunomodulation, and bone marrow transplantation. Multiple myeloma is very sensitive to chemotherapy, which is the primary treatment method. The choice of chemotherapy depends on several factors, such as a patient's age, likelihood of receiving autologous stem cell transplantation, performance status, and renal function. Patients are divided into 3 main categories: (1) young, potential transplant recipients; (2) high-risk patients with advanced disease who are potential transplant recipients; and (3) elderly patients not suitable for transplantation. In general, the first decision made in the management of patients with myeloma who require systemic therapy is whether stem cell transplantation is part of the strategy.

For the first category of patients, the most commonly used medication combination is lenalidomide and dexamethasone or bortezomib-based treatment with dexamethasone. Lenalidomide, an analogue of thalidomide, provides a better response rate when combined with high-dose dexamethasone than high-dose dexamethasone used alone.[14] In 2003, the US Food and Drug Administration (FDA) approved a proteasome inhibitor, bortezomib, for patients with relapsed myeloma. A randomized trial found bortezomib plus dexamethasone more effective than VAD (vincristine/doxorubicin [Adriamycin]//dexamethasone) for induction. A superior response rate has also been demonstrated when a combination of bortezomib, thalidomide, and dexamethasone was compared with thalidomide plus dexamethasone. Bortezomib also demonstrates a special benefit in patients with plasma cell leukemia and renal failure.[15]

The second category is that of high-risk patients with advanced-stage disease. These patients represent approximately 25% of those with newly diagnosed multiple myeloma, and these patients tend to have a shorter overall survival. They respond to traditional therapies for induction but tend to relapse rapidly. The use of thalidomide, lenalidomide, and bortezomib has improved outcomes for this high-risk group.

One typical regimen is bortezomib/lenalidomide/dexamethasone; bortezomib is administered with intravenous push at 1.3 mg/m2 IVP on days 1, 4, 8, and 11, plus lenalidomide orally administered at 25 mg daily on days 1-14, plus dexamethasone administered orally at 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 or 40 mg orally daily on days 1, 8, and 15. This is on a 21-day cycle for 3 or 4 cycles.

Once a response has been achieved, these patients can be considered for autologous stem cell transplantation.

In 2012, carfilzomib (Kyprolis), a proteasome inhibitor, was approved in United States for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of therapy completion. The approval was based on a phase 2b, single-arm, multicenter clinical study of 266 patients with relapsed multiple myeloma with other therapies. The study assessed for overall response rate, which was 22.9% over a median duration of 7.8 months.[19]

Pomalidomide (Pomalyst), a thalidomide analogue, is also approved for multiple myeloma in patients who have disease progression despite two prior therapies (including lenalidomide and bortezomib). For additional information, see Multiple Myeloma Treatment Protocols.

The third category, which is made up of elderly patients (> 70 years) not qualifying for stem cell transplantation, are usually given combination therapy with one of the commonly used regimens -- depending on a patient's clinical condition and risk stratification. Patients who have a relapse after the initial disease is controlled may be treated with any agent not already used. If the disease relapses 6 months after initial therapy, then the initial regimen can be used again. Patients with refractory myeloma are treated with conventional chemotherapy or autologous stem cell transplantation. The use of combinations and targeted therapies has improved responses in these patients.[16]

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