The availability of drugs such as thalidomide, bortezomib and lenalidomide changed the landscape in myeloma treatment and has extended the median survival up to 10 years with a substantial improvement in quality of life. This development prompted a Swiss expert panel to re-evaluate the current status and formulate updated clinical recommendations for the diagnosis and treatment of plasma cell myeloma. These recommendations should help clinicians in their decision making to achieve the best outcome based on currently available data.
Purpose The objective of this randomized trial was to assess the efficacy and safety of rituximab as in vivo purging before transplantation and as maintenance treatment immediately after high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in patients with relapsed follicular lymphoma (FL). Patients and Methods Patients with relapsed FL who achieved either complete or very good partial remission with salvage chemotherapy were randomly assigned using a factorial design to rituximab purging (P+; 375 mg/m 2 once per week for 4 weeks) or observation (NP) before HDC-ASCT and to maintenance rituximab (M+; 375 mg/m 2 once every 2 months for four infusions) or observation (NM). Results From October 1999 to April 2006, 280 patients were enrolled. The median age was 51 years (range, 26 to 70 years), and baseline characteristics were well balanced between groups. On average, patients were 44 months (range, 3 to 464 months) from diagnosis, with 79% having received two lines and 15% three lines of prior therapy. Median follow-up was 8.3 years. In contrast to purging, 10-year progression-free survival (PFS) was 48% for P+ and 42% for NP groups (hazard ratio [HR], 0.80; 95% CI, 0.58 to 1.11; P = .18); maintenance had a significant effect on PFS (10-year PFS, 54% for M+ and 37% for NM; HR, 0.66; 95% CI, 0.47 to 0.91; P = .012). Overall survival (OS) was not improved by either rituximab purging or maintenance. Conclusion Rituximab maintenance after HDC-ASCT is safe and significantly prolongs PFS but not OS in patients undergoing transplantation for relapsed FL. Pretransplantation rituximab in vivo purging, even in rituximab-naive patients, failed to improve PFS or OS.
Purpose To investigate neoadjuvant chemotherapy with cisplatin and gemcitabine followed by extrapleural pneumonectomy with or without radiation therapy in patients with potentially resectable malignant pleural mesothelioma (MPM). Patients and Methods Eligible patients had MPM with clinical stage T1-3, N0-2, M0 disease considered to be completely resectable and a WHO performance status of 0 to 2. Neoadjuvant chemotherapy consisted of three cycles of cisplatin 80 mg/m 2 on day 1 and gemcitabine 1,000 mg/m 2 on days 1, 8, and 15, given every 28 days. Surgery had to consist of a complete extrapleural pneumonectomy, including resection of pericardium and diaphragm. Postoperative radiotherapy was to be considered for all patients. Results Nineteen patients with MPM were included in this pilot study. According to the European Organization for Research and Treatment of Cancer prognostic score, two patients were in the good prognosis group, and 17 patients were in the poor prognosis group. The response rate to neoadjuvant chemotherapy was 32%. The major toxicity was thrombocytopenia. Extrapleural pneumonectomy was performed in 16 patients with no perioperative mortality. Major surgical complications occurred in six patients, and all were treated successfully. Thirteen patients received postoperative radiotherapy. The median survival time was 23 months. Two patients remain alive and free of disease 41 and 38 months after initiation of therapy. Conclusion For patients with potentially operable MPM, the availability of active and well-tolerated chemotherapy regimens, the fact that extrapleural pneumonectomy can be safely performed after neoadjuvant chemotherapy in an experienced center, and the promising results regarding survival in our pilot study warrant further investigation of the role of neoadjuvant chemotherapy in a multimodality strategy.
durable complete remission (rate, 57%) after dose-intense sequential, accelerated chemotherapy with paclitaxel ifosfamide and three cycles of high-dose carboplatin etoposide (mean target carboplatin area under the curve [AUC] of 24 [mg/mL] minute per cycle) followed by peripheral blood-derived stem-cell support in patients with cisplatin-resistant germ cell tumors. Hearing impairment or deafness were not reported as adverse effects. Carboplatin-induced ototoxicity in different high-dose combination regimens has been described by other investigators [2,3]. Between October 2000 and August 2002, we treated nine patients with resistant or recurrent germ cell tumors according to the regimen described by Motzer et al, with three cycles of high-dose carboplatin etoposide (carboplatin AUC of 24 [mg/mL] minute). All patients were pretreated with as many as four cycles of cisplatin-containing chemotherapy. At the beginning of the dose-intense therapy, none of the patients had a clinically obvious hearing impairment. During treatment, all of them started to suffer from hearing disorders and finally developed a clinically manifested hearing impairment. Audiometry revealed bilateral high-frequency sensorineural hearing loss (above 2,000 Hz), with tinnitus in six patients; three of them needed a hearing aid. Hearing impairment was apparent in the other three patients as well, though audiometry was not done. Our experience confirms the favorable results in this group of patients with poor prognosis (five of nine patients are in durable complete remission; complete remission rate, 56%), whereas the ototoxicity observed with this regimen is a considerable adverse effect. Ototoxicity seems to be strongly related to the cumulative carboplatin AUC [3]. High-dose carboplatin is thought to be important to obtain favorable results in patients with relapsed or resistant germ cell tumors. Clinicians should be aware of the possible severe ototoxicity with this regimen, and patients undergoing multiple cycles of carboplatin-containing high-dose chemotherapy should be informed about this relevant toxicity.
Introduction: It is well established that follicular lymphoma (FL) patients who have progression of disease within 24 months (POD24) from frontline immunochemotherapy have worse overall survival (OS) and thus constitute a high-risk population (Casulo et al. J Clin Oncol 33:2516-2522, 2015; Jurinovic et al., Blood 128:1112-1120, 2016). Thus far, however only one report from the Nordic Lymphoma Group (NLG) has shown, without an independent validation cohort, that this endpoint can be useful also to predict the long term survival of patients receiving systemic treatment with chemotherapy-free regimens (Lockmer et al. J Clin Oncol 36:3315-3323, 2018). In the present study, we sought to confirm that early progression after first-line treatment is affecting OS also in patients initially treated with immunotherapy only. Methods: In order to determine whether POD24 is associated with inferior OS, we analyzed a pooled dataset of three randomized trials including FL patients with advanced and symptomatic disease conducted between 1998 and 2016 by the Swiss Group for Clinical Cancer Research (SAKK), namely the SAKK35/98 and 35/03 studies, which evaluated different durations of rituximab therapy, and the SAKK 35/10 study, which compared rituximab monotherapy versus rituximab plus lenalidomide in the front-line therapy. OS was calculated from disease progression in patients with POD24 and from 24 months after the start of treatment in the reference group of those without POD24. Results: A total number of 521 FL patients were enrolled in the three SAKK studies, 333 of them had no prior systemic treatment (64 in the SAKK 35/98, 115 in the SAKK 35/03 and all 154 in the SAKK 35/10 studies, respectively) and received front-line therapy with Rituximab alone (n=256) or in combination with lenalidomide (n=77). We excluded 1 patient from the analysis who died without progression within 24 months and 14 other patients who were lost to follow-up without progression within 24 months from treatment start. Hence, the final cohort of this study comprised 318 evaluable patients. POD24 was observed in 85 of 318 (27% [95%-CI: 22, 32]) patients initially treated without chemotherapy. Patients with POD24 showed a trend towards more advanced disease at presentation than the reference group without POD 24: stage IV (55% vs 43%), B-symptoms (26% vs 17%), bulky disease (44% vs 35%), but the differences did not reach the statistical significance. In patients with early POD, median age was 59 years, 42 patients were male (49%) and 43 female (51%), and 20 had elevated LDH (24%). In the reference group of patients without POD24, median age was also 59 years, 97 patients were male (42%) and 136 female (58%), and 48 had elevated LDH (21%). Figure 1 shows the Kaplan-Meier estimates of survival according to POD24. Median survival was not reached in either of the treatment groups. The patients experiencing POD24 had 5- and 10-year OS rates of 69% and 59%, respectively, while in the reference group the 5- and 10-year OS rates were 92% and 77% (HR = 3.12 [1.73, 5.65]; log-rank P < 0.0001). In a multivariable Cox model POD24 predicted poor survival (P=0.0355) across all studies irrespectively of LDH value, presence of B-symptoms or advanced stage. FLIPI score and beta2-microglobulin values were available only in the SAKK 35/10 study and could not be included in the model. Keywords: follicular lymphoma (FL); rituximab. Disclosures: Moccia, A: Consultant Advisory Role: Takeda, Roche, Janssen. Taverna, C: Consultant Advisory Role: Takeda, Celgene, Janssen, AMGEN; Research Funding: Celgene. Kimby, E: Consultant Advisory Role: Roche, Celgene; Honoraria: Roche, Celgene; Research Funding: Roche.
