8. African Americans with translocation t(11;14) have superior survival after autologous hematopoietic cell transplantation for multiple myeloma in comparison with Whites in the United States -Badar --Cancer -Wiley Online Library [Internet]. [cited 2020 Nov 16].
BACKGROUND Bendamustine and Rituximab (BR) therapy is recommended in international consensus guidelines for treatment of Waldenström Macroglobulinaemia (WM) in both frontline and relapsed settings. The optimal dose and schedule of Bendamustine is not well established. Dose options include 90mg/m2 or 70mg/m2 on days 1&2 of each of 6 cycles (total Bendamustine dose of 1080mg/m2 and 840mg/m2, respectively) +/- reduction from 6 to 4 cycles. AIMS Determine response rates (IWWM criteria), PFS and toxicity following BR in frontline and relapsed settings Determine the impact of depth of response and Bendamustine dose on PFS METHODS A multicentre, retrospective cohort analysis was undertaken of consecutive WM patients treated with BR in the frontline or relapsed settings. Data were collected from 17 sites across 4 countries, including UK centres participating in the Rory Morrison Registry. RESULTS Data from Sep 2010 to May 2020 were collected for 250 patients. Frontline (n=139, 55.6%) and relapsed (n=111, 44.4%) cohorts were matched in terms of sex, age at commencement of BR, ECOG score, and baseline parameters including: haemoglobin, platelet count, bone marrow infiltration, and presence of adenopathy, splenomegaly and extranodal disease. At a median follow up of 37 months, disease progression had occurred in 25 frontline patients (18.0%) and 48 relapsed patients (43.2%; p<0.001). Death due to all causes had occurred in 16 frontline (11.5%) and 40 relapsed patients (36.0%; p<0.001). Major responses (≥PR) differed significantly between frontline and relapsed cohorts (91.4% vs 73.9%, respectively; p<0.001), as did objective responses (≥MR; 97.8% vs 83.8%; p<0.001) and combined CR/VGPR rates (47.4% vs 24.3%; P<0.001). ECOG score, age and presence of extranodal disease were also predictors of response. Best response significantly impacted on PFS and OS. Two-year predicted PFS rates for those achieving CR/VGPR vs PR were 96% vs 82%, respectively (p=0.002, Fig. 1A). Median OS was 83 months after achieving CR/VGPR, 65 months after achieving PR/MR and 28 months after achieving SD/PD (p<0.001). Relapsed patients had received 1 (n=53, 47.7%), 2 (n=28, 25.2%) or ≥3 (n=30, 27.0%) prior therapies. PFS was significantly longer in the frontline cohort compared with recipients of ≥2 prior lines of treatment, but not between cohorts treated frontline vs after 1 prior therapy line (Fig. 1B). Rates of toxicity-related treatment truncation were significantly lower in the frontline setting (17.3% vs 35.1%; p<0.001). Frontline patients received higher total Bendamustine doses than relapsed patients (median total dose 1080mg/m2 vs 720mg/m2; p<0.001), and dose was independently predictive of PFS. In the frontline setting, PFS was superior in the group receiving ≥1000mg/m2 (i.e. 90mg/m2 on days 1&2 for 6 cycles) compared with those receiving 800-999mg/m2 (p=0.04); two-year predicted PFS rates were 95% and 89%, respectively (Fig. 1C). In the relapsed cohort, by contrast, there was no PFS difference between the ≥800mg/m2 and the 600-799mg/m2 dose groups (p=0.19). Those who received doses of <600mg/m2 (i.e. ≤70mg/m2 on days 1&2 for 4 cycles, or less) had significantly poorer PFS outcomes compared with those who received ≥600mg/m2 (p=0.01), with two-year predicted PFS rates of 75% and 46%, respectively (Fig. 1D). Age did not significantly affect tolerated dose in the frontline cohort, with similar median total Bendamustine doses in the <75-year and ≥75-year groups. Of note, 12/17 frontline patients aged ≥80 years received doses of ≥720mg/m2 (4-6 cycles with a starting dose of 90mg/m2). Older relapsed patients tolerated lower total Bendamustine doses: median dose received by subjects aged <65 years was 900mg/m2, compared with 720mg/m2 (65-74 years) and 540mg/m2(≥75 years). CONCLUSION Outcomes for WM patients following BR are excellent. Frontline patients tolerate higher doses of Bendamustine, and achieve deeper responses and longer PFS than relapsed patients. In both settings, attaining CR/VGPR results in superior PFS and OS. Our data clearly delineate the Bendamustine doses required to achieve optimum PFS. At frontline, 6 cycles of 90mg/m2 on days 1&2 is superior to lower doses with respect to response and PFS. In the relapsed cohort, maximum response and PFS benefit are seen with 4 cycles of 90mg/m2 on days 1&2; a starting dose of 70mg/m2 on days 1&2 is also sufficient provided 5-6 cycles are administered. Disclosures Menne: Kyowa Kirin: Other: Travel expenses; AstraZeneca: Research Funding; Pfizer: Honoraria, Other; Atara: Honoraria; Novartis: Honoraria, Research Funding; Kite/Gilead: Honoraria, Other: Travel expenses; Celgene: Honoraria, Other: Travel expenses; Daiichi Sankyo: Honoraria; Amgen: Honoraria, Other: Travel expenses; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Bayer: Other: Travel expenses; Roche: Honoraria. Talaulikar:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding. Pratt:Binding Site Ltd: Other: Personal fees; Amgen: Other: Personal fees; Janssen: Other: Personal fees; Celgene: Other: Personal fees; Takeda: Other: Personal fees; Gilead: Other: Personal fees; Sanofi-Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Manos:Bristol-Myers Squibb: Other: Conference sponsorship. Gavriatopoulou:Genesis Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Minnema:Kite, a Gilead Company: Speakers Bureau; Celgene: Other: travel support, Research Funding; Servier: Consultancy; Amgen: Consultancy. El-Sharkawi:Roche: Other: Conference fees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kersten:Kite, a Gilead Company: Consultancy, Honoraria, Other: travel support; Novartis: Consultancy, Honoraria, Other: travel support; Miltenyi: Consultancy, Honoraria, Other: travel support; Roche: Research Funding; Takeda: Research Funding; Celgene: Research Funding. McCarthy:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria. Bishton:Janssen: Consultancy; Takeda: Other: Travel/accommodations/expenses, Research Funding; Roche: Other: Travel/accommodations/expenses, Research Funding; Gilead: Other: Travel/accomodations/expenses, Research Funding; AbbVie: Research Funding. Follows:Roche: Consultancy, Other: Paid lecturing; Karyopharm: Consultancy, Other: Paid lecturing; Janssen: Consultancy, Other: Paid lecturing; Abbvie: Consultancy, Other: Paid lecturing; Bristol Myers Squibb: Consultancy, Other: Paid lecturing; Astrazeneca: Consultancy, Other: Paid lecturing. Wechalekar:Janssen, Takeda, Caelum, Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. D'Sa:BeiGene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Sanofi: Honoraria.
Background Reversal of warfarin with prothrombin complex concentrates (PCC) is required in cases of significant bleeding or need for urgent surgery. A weight‐based regimen is commonly, but a fixed‐dose approach is also feasible with clinically equivalent outcomes. The purpose of this audit is to review the clinical and laboratory outcomes of patients treated in our centre where fixed‐dose PCC is used for warfarin reversal. Aims The primary objective was to evaluate the post‐reversal international normalised ratio (INR). The secondary objectives were the proportion of patients requiring repeat PCC and 30‐day complication rates (death, haemorrhage and thrombosis). A subgroup analysis was also performed to compare the outcomes of those who received a dose of ≤15 IU/kg (reduced dose) with those who received >15 IU/kg (standard dose). Methods Patients who received three‐factor PCC for warfarin reversal between 1 January and 31 December 2016 were identified and analysed. Clinical data and PCC dosages were extracted from electronic patient records. Results A total of 144 patients were analysed. The median INR pre‐reversal was 3.25 (range 1.4–10), which reduced to 1.5 (0.9–3.0) post‐reversal. Eighty‐seven percent of patients achieved a post‐reversal INR of less than 2 and 55% less than 1.5. Sixteen patients required a repeat dose. Complications occurred in 22 (15.3%) patients, which consisted of 15 deaths, 7 thrombosis and 2 haemorrhage. No statistically significant differences in the primary and secondary outcomes were noted between reduced‐dose and standard‐dose subgroups. Conclusion Our results support the use of fixed‐dose PCC for warfarin reversal in a day‐to‐day clinical practice in a hospital setting.
Background: Myeloma patients receiving current first line therapies do significantly better than historically treated patients. However, patients who fail these more effective therapies are difficult to treat. A greater proportion of patients have poor tumour biology, resulting in lower response rates and shorter duration of response. Teniposide, when studied originally in the 1980’s, achieved a response rate of 33% as a single agent in relapsed myeloma. When it was given in combination with dexamethasone and cyclophosphamide, the response rate was up to 73% in heavily pre-treated patients. It has been used in New Zealand for a number of years as second or third line therapy in myeloma, but usage was low and the drug was commercially withdrawn from availability in New Zealand in 2009. In 2012, an alternative source of teniposide was found, and use was restarted in patients who failed bortezomib and iMID (thalidomide and/or lenalidomide) therapy. This is a retrospective analysis of a single centre experience in managing heavily pre-treated myeloma patients with teniposide based chemotherapy, given in combination with cyclophosphamide and prednisone (TCP chemotherapy). Method: Patients with myeloma were identified using the patient electronic database. Consecutive patients who were treated with TCP chemotherapy between 1 January 2012 and 1 July 2014 were included. Cycles were given every 3-6 weeks depending on count recovery and marrow reserve, and up to 6 cycles were given. Relevant clinical data were gathered from patients’ electronic clinical records. Data were analysed using IBM SPSS Statistics 20. Results: In our cohort, 23 heavily pre-treated patients received TCP chemotherapy. Baseline patient characteristics are shown in table 1. Median follow-up was 7.1 months. The median age was 62 years, and 73.9% were male. Eight patients (34.8%) had adverse cytogenetics. The median number of prior regimens was 3 (range 1 - 7). Prior bortezomib was given in 19 (82.6%), 19 (82.6%) had received thalidomide, 12 (52.2%) had receive lenalidomide, 4 (17.4%) had previous carfilzomib, and 18 (78.3%) had prior autologous HSCT. Twelve patients (52.2%) completed 4-6 cycles of TCP. Of the remaining 11 patients, 3 (27.3%) were still receiving active TCP chemotherapy at the time of analysis and had only completed 1 to 2 cycles, 4 (36.4%) did not respond and were switched to a different regimen, 3 (27.3%) died after the first cycle, and 1 progressed and died after the second cycle. Treatment response, as shown in the waterfall plot (figure 1), was evaluated in 20 of the 23 patients (3 patients died prior to repeat paraprotein levels were done). The overall response rate, including minor response, was 55% (11/20) and ≥ PR was seen in 30% (3 had PR, 3 had VGPR). Three (15%) patients had progressive disease during TCP chemotherapy. The median time to progression for the 17 patients with VGPR, PR or stable disease was 5.2 months. During the follow-up period, 12 of the 23 patients died (52.2%). Ten died due to disease progression, 1 from TCP related toxicity (infection), and 1 died from an unrelated issue. For all cause mortality, the median overall survival was 6.1 months. Conclusion: TCP chemotherapy was well tolerated with more than half of the patients completing 4-6 cycles, and only one died from TCP related toxicity. In our heavily pre-treated cohort, over half had their disease held at bay for the duration of the TCP treatment. This result is comparable to that published for pomalidomide and dexamethasone in a similar patient cohort. While there are a number of promising new agents being developed, older therapies, such as TCP, should not be overlooked, as it is an effective regimen even if patients have failed proteosome inhibitors and iMID therapy. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Simpson: Onyx: Honoraria, Research Funding; Celgene: Honoraria; Janssen Cilag: Honoraria.
Bendamustine and rituximab (BR) therapy is commonly used in the treatment of Waldenström Macroglobulinemia (WM). The impact dose of Bendamustine dose on response and survival outcomes is not well‐established, and the impact of its use in different treatment settings is not clear. We aimed to report response rates and survival outcomes following BR, and clarify the impact of depth of response and bendamustine dose on survival. A total of 250 WM patients treated with BR in the frontline or relapsed settings were included in this multicenter, retrospective cohort analysis. Rates of partial response (PR) or better differed significantly between the frontline and relapsed cohorts (91.4% vs 73.9%, respectively; p < 0.001). Depth of response impacted survival outcomes: two‐year predicted PFS rates after achieving CR/VGPR vs PR were 96% versus 82%, respectively (p = 0.002). Total bendamustine dose was predictive of PFS: in the frontline setting, PFS was superior in the group receiving ≥1000 mg/m2 compared with those receiving 800–999 mg/m2 (p = 0.04). In the relapsed cohort, those who received doses of <600 mg/m2 had poorer PFS outcomes compared with those who received ≥600 mg/m2 (p = 0.02). Attaining CR/VGPR following BR results in superior survival, and total bendamustine dose significantly impacts response and survival outcomes, in both frontline and relapsed settings.
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