38: MULTIPLE MYELOMA/PLASMACYTOMA
Jerry T. Liu, MD
Rahul R. Parikh, MD
WORKUP
All Cases
H&P
Labs—CBC with differential, complete metabolic panel, LDH, beta-2-microglobulin, serum free monoclonal light chain (FLC), 24-hour urine protein, serum/urine protein electrophoresis, and immunofixation
Imaging—Skeletal survey, if bone pain with negative XR or compression fracture: noncontrast CT, PET-CT, MRI
Biopsy—unilateral bone marrow aspiration and biopsy with immunophenotyping, cytogenetics, and FISH analysis
International Myeloma Working Group (IMWG) Criteria for Active (Symptomatic) Multiple Myeloma (MM)
(a) Clonal bone marrow plasma cells ≥10% or biopsy-proven plasmacytoma and (b) ≥1 of the following criteria: hypercalcemia, renal insufficiency, anemia, lytic bone lesion(s) on XR, CT, or PET-CT or ≥1 biomarker of malignancy:(≥60% clonal plasma cells, FLC ratio uninvolved:involved ≥100, >1 focal lesions on MRI)
IMWG Criteria for Smoldering (Asymptomatic) MM
(a) serum M-protein ≥3 g/dL, urine M-protein ≥500 mg per 24 hour and/or 10% to 60% bone marrow plasma cells, (b) no myeloma-defining events or amyloidosis
Criteria for Solitary Plasmacytoma (SP)
(a) biopsy proven single bone/soft tissue lesion, (b) normal bone marrow, (c) negative skeletal survey and MRI spine/pelvis, and (d) no anemia, hypercalcemia, and renal insufficiency
Consideration for Bisphosphonate Therapy
Bone densitometry
Consideration for Allogeneic Transplant
HLA typing
TREATMENT RECOMMENDATIONS BY DISEASE AND STAGE
SP |
Bone: RT alone Extramedullary: RT and/or surgery |
Smoldering MM |
Surveillance (3–6 m interval) |
Active MM (up to 40% cases will get RT) |
Systemic therapy + bisphosphonate (evaluate response at two cycles) then consider for stem cell transplant ±RT ± surgery ± maintenance systemic therapy RT indications: Uncontrolled pain, impending pathologic fracture, and cord compression |
TECHNICAL CONSIDERATIONS
Simulation
Immobilization and setup based on site of lesion. Wire superficial lesions + margin.
Dose Prescription
SP
RT ≥45 Gy in 1.8 to 2 Gy/fx (recent data suggest lower doses may be appropriate)
MM
Single fraction (8 Gy) or RT 10 to 30 Gy in 2 to 5 Gy/fx, boost to ≥36 Gy for bulky disease, cord compression, or partial response. Commonly used prescription for palliation is 20 Gy in 10 fractions.
Target Delineation
For vertebral SP or MM, consider covering one uninvolved body earlier and in the following.
SP
GTV = visible lesion on all available imaging (e.g., MRI, PET-CT, pre-op scans)
CTV = GTV + 2.0- to 3.0-cm margin (Elective nodal coverage for extramedullary SP should be considered)
PTV = CTV + 0.3- to 0.5-cm setup error
MM
Symptomatic lesion + margin, avoid uninvolved pelvic and long bones to preserve bone marrow.
Treatment Planning
SP
3D, intensity-modulated radiation therapy (IMRT), or stereotactic body radiation therapy (SBRT) (based on site)
MM
Typically opposed fields, more complex if needed
Energy (6–10 MV) based on location
FOLLOW UP
SP
Myeloma labs every 3 to 6 months, bone marrow aspirate and biopsy and imaging if indicated (>50% patients with bone SP progress to MM, <50% patients with extramedullary SP progress to MM)
MM
Myeloma labs every 3 months, skeletal survey annually or with symptoms, bone marrow aspirate and biopsy and imaging if indicated.
SELECTED STUDIES
Düsseldorf MM (Matuschek, Radiat Oncol 2015; DOI: 10.1186/s13014-015-0374-z)
Retrospective.107 patients with MM treated with palliative RT from 1989 to 2013. Median dose 25 Gy (range 8–50 Gy). Pain relief 85% (31% complete, 54% partial). Higher dose RT (30 Gy vs. 20 Gy) was associated with higher rate of pain relief and bone recalcification.
Spinal Cord Compression MM (Rades, Int J Radiat Oncol Biol Phys 2006; DOI: 10.1016/j.ijrobp.2005.10.018)
Retrospective. International, multi-institutional.172 patients with MM treated with RT for SCC. 61 received short-course RT (8 Gy × 1, 4 Gy × 5) and 111 received long-course RT (3 Gy × 10, 2.5 Gy × 15, 2 Gy × 20). Median survival 17 months, LC 92%. More durable motor function improvement with long-course RT regimens, higher EQD2 (>30 Gy).
MDACC SP (Reed, Cancer 2011; DOI: 10.1002/cncr.26031)
Retrospective. 84 patients with SP (59 bone, 25 extramedullary) treated with definitive RT from 1988 to 2008. Median dose 45 Gy (range 36–53.4 Gy). Five-year overall survival (OS) 78%, LC 92%, progression to MM 47%. Predictors of progression: bone site and serum protein at diagnosis. Seven patients had LR (two marginal, five in-field), no correlation with dose.
Multicenter SP (Ozsahin, Int J Radiat Oncol Biol Phys 2006; DOI: 10.1016/j.ijrobp.2005.06.039)
Retrospective. 19 European and North American centers (Rare Cancer Network). 258 patients with SP (206 bone, 52 extramedullary) treated from 1977 to 2001, Median dose 40 Gy (range 20–66 Gy), no elective nodes treated. Five-year OS 74%, LC 86%, progression to MM 45%. Predictors for progression to MM: bone site. No dose-response for doses >30 Gy.
Extramedullary SP (Alexiou, Cancer 1999; DOI: 10.1002/(SICI)1097-0142(19990601)85:11<2305::AID-CNCR2>3.0.CO;2-3)
Literature Review. 869 patients with extramedullary SP (714 in upper aerodigestive tract [UAD] and 155 non-UAD) treated with either RT alone, surgery + RT, or surgery alone. Significantly higher OS and RFS with combined therapy for patients with UAD lesions. No survival difference between treatments for non-UAD lesions.