Single Solitary Plasmacytoma to Active Myeloma

Presentation

The patient is a 77-year-old male with a history of solitary plasmacytoma (SP) who was diagnosed in 2011 when he presented with a T12 mass. A complete work-up revealed an IgG kappa myeloma protein, although there were no other criteria to indicate active myeloma. Of note, he had 9% plasma cell involvement on his initial work-up. He received radiation to his T12-L2 at a dose of 44 Gy in 22 fractions, in the spinal nerve roots down to the inferior thecal sac for a total of 36 Gy. He was followed routinely with labs and imaging with no further issues until November 2020, when he developed multiple new ¹⁸F-fluorodeoxyglucose (FDG)-avid osseous lesions throughout the axial and appendicular skeleton, including the bilateral humeri, sternum, thoracic and lumbar spine, multiple bilateral ribs, pelvic bones, and bilateral femurs as found on PET/CT. His labs revealed a detectable IgG paraprotein at 0.20 g/dL, free kappa light chain of 20 mg/L. His blood counts and calcium were unremarkable, and his bone marrow biopsy had less than 5% plasma cells, although a small population of plasma cells noted kappa light chain restriction by flow, indicating symptomatic IgG kappa myeloma. Fluorescence in situ hybridization (FISH) and cytogenetics were normal.

In December 2020 the patient started on daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-VRd). He received 4 cycles, followed by stem cell mobilization and autologous stem cell transplant (ASCT). He also started on monthly zoledronic acid with induction as well as DVT prophylaxis with a daily 81mg aspirin, an antiviral, and Pneumocystis jirovecii pneumonia (PJP) prophylaxis with sulfamethoxazole/trimethoprim. At day 100 post-transplant, he had achieved a stringent complete response (sCR), and the risks and benefits of maintenance were discussed. He started on lenalidomide 10 mg on days 1-21 on a 28-day cycle. He was otherwise in very good health, his only other health issue being well-controlled hypertension. 

The patient continues to be followed up with labs and routine PET/CTs and continues in sCR. He experienced grade 1 peripheral neuropathy to both feet and his lenalidomide maintenance was decreased to 5 mg on days 1-21 on a 28-day cycle with no further issues. As part of his supportive care, he also continued taking a daily 81 mg aspirin, as well as valacyclovir 500 mg daily. He was also on PJP prophylaxis for 6 months post-transplant. He completed 1 year of monthly zoledronic acid and then decreased to every 3 months. At 2 years post-transplant he continued in sCR, with no minimal residual disease (MRD); zoledronic acid was discontinued.

Treatment Rationale

Cases like the patient discussed above are not common, but they are seen from time to time. The patient received radiation, which is typical, as SPs are known to be highly sensitive to radiation. The patient did well for about 9 years before progressing to symptomatic myeloma. He was followed routinely with quarterly labs and PET/CTs about every 6 months. He had minimal plasma cell involvement at initial diagnosis, which put him at higher risk for progression to symptomatic myeloma within 10 years of diagnosis.

Induction therapy with D-VRd was the standard induction regimen based on the phase II GRIFFIN trial data.¹ He tolerated treatment well without toxicities and completed 4 standard induction cycles. He did not have neuropathy at this point, although he did develop mild cold sensation to both feet following stem cell mobilization. He underwent ASCT without issues and fell back to his baseline by day 100 post-transplant. Day 100 restaging noted sCR with no detectable disease. He started lenalidomide 10 mg maintenance at this point, although he later was reduced to 5 mg based on grade 1 peripheral neuropathy to both feet.

The multi-team approach continues to be an effective approach for caring for myeloma patients. Knowing the potential risk of developing symptomatic myeloma, close monitoring of this patient was essential. Much education was needed upfront when he presented with SP and then reinforced over years of monitoring. When he relapsed with symptomatic myeloma, he initially struggled with the need to start systemic therapy and the thought of continuous treatment. APPs typically see and monitor patients throughout their treatment and play an important role in the discussion and management of treatment and potential side effects.

Discussion

Solitary plasmacytoma is a rare localized plasma cell disorder, occurring in <5% of patients or an incidence of about 450 cases annually.^2,3 These patients do not have evidence of systemic myeloma, so there’s an absence of CRAB criteria (hypercalcemia, renal failure, anemia, and bone disease) and it is important to discern whether there is minimal bone marrow involvement or not.⁴ Diagnosis of SP versus symptomatic myeloma is shown in Table 1. SPs can present as a solitary bone plasmacytoma (SBP) or a solitary extramedullary plasmacytoma (SEP) which is based in the soft tissues. SEPs can develop in any soft tissue, although they are most common in the head and neck region, lungs, and gastrointestinal tract. At about 70%, SBPs are more common and are primarily found in the spine, femurs, pelvis, and ribs.⁵ These patients are at risk of developing symptomatic myeloma after diagnosis. Patients who present with SBP, especially those with minimal bone marrow detection, have a higher risk of progression to active myeloma. About 50% of patients with SBP and 30% with SEP will develop symptomatic myeloma within 10 years of diagnosis.^5,6

 Table 1 Diagnostic criteria for solitary plasmacytoma (Caers et al.)

Radiation has been the standard therapy for SPs as plasmacytomas are known to be highly responsive to radiotherapy (RT). Most of the data on the effectiveness of radiation are based on retrospective studies. Multiple studies have demonstrated that RT is more effective than surgery in this population of patients, although there is a lack of studies with large number of patients due to the low incidence.^2,4,5 Curry et al. retrospectively reviewed the longitudinal impact of RT on disease control, progression, and survival and found that SPs can be locally controlled through RT and that SBP progression to symptomatic myeloma over SEP was consistent with published data.

This case is an example of a rare occurrence of single solitary plasmacytoma that an APP may see in their clinical practice. It’s important to understand the differences between SP and symptomatic myeloma when monitoring the disease and discussing a treatment plan with the patient. Once worked up and confirmed, radiation is the standard approach and then ongoing disease assessment. While single bone plasmacytomas represent the majority of all SP cases, patients can also present with extramedullary involvement, and both are at risk of developing into symptomatic myeloma. APPs play a significant role in the ongoing monitoring, discussion, and management of these patients in clinical practices.

References

1. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288
2. Curry J, O'steen L, Morris CG, Kirwan JM, Mendenhall WM. Long-term outcomes after definitive radiation therapy for solitary plasmacytoma. Am J Clin Oncol. 2020;43(10):709-713. doi:10.1097/COC.0000000000000734
3. Thumallapally N, Meshref A, Mousa M, Terjanian T. Solitary plasmacytoma: population-based analysis of survival trends and effect of various treatment modalities in the USA [published correction appears in BMC Cancer. 2017 Jun 23;17 (1):443]. BMC Cancer. 2017;17(1):13. Published 2017 Jan 5. doi:10.1186/s12885-016-3015-5
4. Pham A, Mahindra A. Solitary plasmacytoma: a review of diagnosis and management. Curr Hematol Malig Rep. 2019;14(2):63-69. doi:10.1007/s11899-019-00499-8
5. Caers J, Paiva B, Zamagni E, et al. Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel. J Hematol Oncol. 2018;11(1):10. Published 2018 Jan 16. doi:10.1186/s13045-017-0549-1
6. Kilciksiz S, Karakoyun-Celik O, Agaoglu FY, Haydaroglu A. A review for solitary plasmacytoma of bone and extramedullary plasmacytoma. ScientificWorldJournal. 2012;2012:895765. doi:10.1100/2012/895765