Background:
Solitary plasmacytoma (SPC) is a rare plasma cells disorder, which may present as a single bone lesion or an extramedullary plasmacytoma. High dose radiotherapy may be curative, yet most ...patients eventually develop Multiple Myeloma (MM). Due to rarity of the disease, there is uncertainty regarding the optimal treatment strategy, especially in patients that present with known risk factors. The role of adjuvant anti-myeloma therapy is still under debate, whereas few studies have reported efficacy of novel agents.
We aimed to explore clinical characteristics and treatment patterns and to identify predictors for relapse and progression to myeloma in a real world setting.
Methods:
Consecutive patients, diagnosed and treated for solitary plasmacytoma in 13 centers, between 2008 and 2019 (defined by the IMWG criteria) were identified, based on medical centers patient registries and pathological reports. Patient's medical charts were reviewed, and data regarding patient and disease characteristics, treatment regimen, and clinical endpoints, focusing on response to treatment and time to disease progression were documented. The treatment response categories were defined according to the IMWG criteria.
Results:
62 patients (pts) were identified. Baseline characteristics and workup are detailed in the table. Median follow-up was 39 months (mo) (IQR: 13.5, 63.3). Fifty nine pts (95.2%) were treated with radiotherapy, with a median dose of 45.0 Gy (range: 30-54 Gy); radiotherapy dose was 45-54 in 31 pts, < 45Gy in 11 pts. Twenty pts (33.9%) underwent surgery in addition to radiotherapy, 3 more pts underwent a surgery alone. The median time to radiotherapy since diagnosis was 2.7 months (range: 1day-18.2 months), 8 pts received any anti-myeloma therapy for treatment of plasmacytoma including Melphalan/dexamethasone (n=1), bortezomib based induction followed by ASCT (n=2), VD/VTD (n=2) and KRD (n=1).
Among 25 patients with evaluable post-therapy PET-CT response (performed 12 months post radiotherapy), 26% had no remaining FDG uptake, 20% had a 50% or greater decrease in FDG uptake. Among 40 patients with CT or MRI post therapy assessment, 20% had disappearance of SPC, 27% had ≥50% reduction, 7% had <50% reduction and 25% remained without change. Non-bone SPC were more likely to achieve CR than bone SPCs, 86% vs 29%, respectively, p=0.021.
During the follow-up period, 16 pts (25.8%) experienced evolution to MM (15 pts had bony and 1 soft tissue plasmacytoma in diagnosis). Among patients with bone SPC (n=49), 30.5% evolved to MM. A total of 6 pts had a recurrence of SPC (5 pts had a bony and 1 patient upper aerodigestive plasmacytoma in diagnosis). 5 pts died (3 without recurrence or evolution to MM). Median time to plasmacytoma recurrence in pts that achieved CR was 36.7 mo (range: 3 -67.9 mo); Median time of evolution to MM was 37.5 mo (range: 6.7-87.2 mo). Progression free survival (PFS) was 67.7 mo for all pts (Fig1A), 48 mo for bone SPC and was not reached for non-bone SPC (p=0.11) (Fig1B). Median overall survival was not reached. Overall survival at median follow-up was 93.6%.
Notably, all 8 pts who were treated with anti-myeloma therapy had a bony plasmacytoma and received radiotherapy in addition. None of these pts had recurrence of plasmacytoma or evolution to MM. Of the 11 pts that had SPC in an upper aerodigestive tract site, none evolved to MM; 10 of these pts were treated with only radiotherapy, one had a plasmacytoma recurrence in the same site.
Conclusions:
We present real world data of a multicenter patient cohort with SPC. As previously suggested, prognosis is more favorable for none bone SPCs. Though numbers are modest, our analysis suggests a benefit of the early addition of systemic therapy to standard radiotherapy for patients with solitary bone plasmacytoma.
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Yael:Janssen: Consultancy; Amgen: Consultancy, Research Funding; Neopharm: Consultancy; Takeda: Consultancy; Madison: Consultancy; VBL Therapeutics: Employment.
Chronic lymphocytic leukemia (CLL) occurs in older individuals with a median age at diagnosis of 72 years. In recent years, there has been considerable progress in the frontline therapy of ...elderly/physically unfit patients with CLL. The German CLL11 trial showed that addition of obinutuzumab to chlorambucil (G-Clb) prolongs progression free survival (PFS) and overall survival (OS) compared to chlorambucil alone or in combination with rituximab. More recently, obinutuzumab together with ibrutinib or venetoclax were shown to be superior to G-Clb with regard to PFS, but there was no advantage in terms of OS.
In this retrospective, multinational and multicenter co-operative study the European Research Initiative on CLL (ERIC) and the Israeli CLL Study Group (ICLLSG) evaluated the efficacy of frontline treatment with G-Clb in patients with CLL, in a “real-world” setting. Our analysis excluded CLL patients with documented del(17p) or TP53 mutations since they are no longer treated with chemotherapy.
Results: A total of 437 treatment-naïve patients with CLL from 51 medical centers located in 13 countries were included. The median age of this patient population was 75.9 years; 59.7% were men, median CIRS total score was 8 and estimated creatinine clearance 61.1 mL/min. Seventy four patients had Binet stage A (17.2%), 167 (38.8%) stage B and 190 (44.1%) stage C. Results of FISH and IGHV mutational status were available for 332 and 115 patients, respectively. High-risk cytogenetics, del(11q) was documented in 18.7% patients and IGHV-unmutated gene in 64.4%. The vast majority of patients were treated with G-Clb (N=408) and the rest with obinutuzumab monotherapy (G-monotherapy, N=29). The clinical overall response was 86.5%, including clinical complete and partial responses in 41.6% and 45.8% of cases, respectively. The median observation time was 14.1 months (m) and the median PFS of the entire cohort was 27.6m (95% CI, 24.2-31.0). The PFS for G-Clb was significantly better than G-monotherapy (P=0.001; HR=0.38, 95% CI: 0.22-0.67), being the 2-year PFS estimates 61.8% and 52.8%, respectively. The median PFS was significantly shorter for patients with del(11q) (19.2m) compared to those with normal FISH (not reached, P<0.001), del(13q) (29.9m, P<0.001) and trisomy12 (not reached, P=0.027). Patients with IGHV-unmutated had a trend for shorter PFS compared to those with IGHV-mutated gene (median PFS 25.3m vs. not reached, respectively. p=0.06). In a multivariate analysis, older age, high risk-disease, lymph nodes >5cm, G-monotherapy, reduced cumulative dose of obinutuzumab and status less than CR, were independently associated with shorter PFS. Seventy patients (16%) received a second-line treatment. The median OS for the entire cohort has not been reached yet and 2-year OS estimate is 88%.
In conclusion, in a “real-world” setting, frontline treatment with G-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were observed in patients with high-risk disease del(11q) and/or IGHV-unmutated and those treated with G-monotherapy. Thus, even today in the era of novel drugs, G-Clb can be considered a legitimate frontline treatment in unfit CLL patients with low-risk disease non-del(11q) and IGHV-mutated.
Herishanu:Roche: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Simkovic:Roche: Honoraria; University Hospital Hradec Kralove: Employment; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Honoraria. Mauro:Gilead: Consultancy, Research Funding; Shire: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Jannsen: Consultancy, Research Funding; Roche: Consultancy, Research Funding. Coscia:Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm Therapeutics: Research Funding. Scarfo:AstraZeneca: Honoraria; Janssen: Honoraria; AbbVie: Honoraria. Tedeschi:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen spa: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; SUNESIS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Honoraria. Gimeno Vázquez:JANSSEN: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Assouline:F. Hoffmann-La Roche Ltd: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau. Levato:Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Rigolin:Gilead: Speakers Bureau; Gilead: Research Funding; AbbVie: Speakers Bureau. Loscertales:Janssen: Honoraria; Roche: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Gilead: Honoraria. Ghia:Dynamo: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria; ArQule: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Juno/Celgene: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; Gilead: Consultancy, Honoraria, Research Funding.
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