Effect of Timing and Duration of Maintenance Lenalidomide in Myeloma Patients after Autologous Stem Cell Transplantations

Abstract Introduction: Maintenance lenalidomide after autologous hematopoietic stem cell transplantation (auto HCT) has been shown to improve progression free (PFS) and overall survival (OS) in myeloma patients. In this analysis we sought to determine the impact of lenalidomide treatment on achievement of complete remission (CR), survival and the incidence of secondary primary malignancies (SPM). Methods: We retrospectively analyzed all (N=466) consecutive myeloma patients who underwent auto HCT and received maintenance lenalidomide between August 2006 and September 2013 at our institution. Patients received doses of maintenance lenalidomide ranging from 5 mg – 15 mg/day or every other day. We looked at whether lenalidomide improved disease status, specifically CR in patients who had not achieved this before maintenance initiation and the median time to achieve CR. We also analyzed the effects of early initiation (<4-months after auto HCT) of maintenance lenalidomide versus late initiation (≥ 4-months after auto HCT) with regards to PFS and OS using the Kaplan-Meier method. Lastly we assessed if continuation of maintenance therapy beyond 2 and 3-years after auto HCT improved PFS and OS and increased the incidence of SPM. Results: The median follow-up time for all patients was 26.6 months. 173 patients (37%) experienced improvements in their disease status. Of these, 86 patients (50% of those with noted improvements and 19% of total patients assessed) who were not in CR before maintenance achieved CR while on maintenance. The average time to achieve CR in these patients was 12.9 months. Comparing the patients who were started on early maintenance treatment with those who were started on late maintenance therapy, we did not find any difference with regards to PFS (Hazard Ratio [HR]=0.90; p-value=0.57) and OS (HR=0.90; p-value=0.74). However, patients who had been on lenalidomide for > 2 years experienced a significant benefit in OS compared with those on lenalidomide for ≤ 2 years (HR=0.36; p-value=0.0015), although no difference in PFS was observed between the two cohorts (HR=0.77; p-value=0.18). A similar trend in OS was seen for patients who had been on lenalidomide > 3 years compared with those on maintenance treatment ≤ 3 years, though not statistically significant (HR=0.47; p-value=0.10). Again, no difference in PFS was noted between the two groups. Lastly there were only 12 cases of SPM reported in all patients assessed with no statistically significant association to the duration of lenalidomide use. In all 12 cases, lenalidomide was suspended and the mortality among these patients was 50%. Conclusions: Maintenance lenalidomide improves response rates after auto HCT in some patients including the CR rate, however, the median time to achieve CR in these patients is approximately 13 months. The patients who received maintenance therapy for > 2years had a significantly lower risk of death with a trend of improved OS in patients who continued maintenance therapy beyond 3-years. We conclude that the maintenance therapy should be continued for at least 2 years and possibly longer after auto HCT. Table 1 Summary of Survival Outcomes Maintenance Treatment Initiation Measure Early (N=155) Late (N=184) p-value Progression-free survival Hazard ratio (95% CI)a 0.90 (0.63, 1.30) 0.57 Overall survival Hazard ratio (95% CI)a 0.90 (0.49, 1.66) 0.74 Duration of Maintenance Treatment Measure > 2 years (N=115) ≤ 2 years (N=224) p-value Progression-free survival Hazard ratio (95% CI)b 0.77 (0.52, 1.13) 0.18 Overall survival Hazard ratio (95% CI)b 0.36 (0.19, 0.67) 0.0015 > 3 years (N=49) ≤ 3 years (N=290) p-value Progression-free survival Hazard ratio (95% CI)b 0.75 (0.45, 1.26) 0.28 Overall survival Hazard ratio (95% CI)b 0.47 (0.19, 1.15) 0.10 a Cox proportional hazards regression model: measure included as a baseline covariate with the following additional covariates: patient’s cytogenetic risk, creatinine, hemoglobin, B2-microglobulin, ISS stage at diagnosis, disease status at auto HCT, and response prior to auto HCT. b Cox proportional hazards regression model: measure included as a time-dependent covariate with the covariates listed above. Figure 1 Comparison of Overall Survival in Early vs Late initiation of Revlimid Figure 1. Comparison of Overall Survival in Early vs Late initiation of Revlimid Figure 2 Overall Survival – All Patients Figure 2. Overall Survival – All Patients Disclosures Shah: Novartis: Consultancy, Research Funding; Millennium Pharmaceuticals: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding; Array: Consultancy, Research Funding. Orlowski:Onyx Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Combined Treatment of Bortezomib, Continuous Low-Dose Cyclophosphamide and Dexamethasone Followed By One Year of Maintenance Treatment for Refractory or Relapsed Multiple Myeloma Patients: A Prospective Phase II Study

Blood ◽

10.1182/blood.v124.21.4733.4733 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4733-4733

Author(s):

Esther GM Waal de ◽

Linda Munck de ◽

Gerhard Woolthuis ◽

Annet velden Van Der ◽

Yvonne Tromp ◽

...

Keyword(s):

Overall Survival ◽

Maintenance Therapy ◽

Research Funding ◽

Low Dose ◽

Progression Free Survival ◽

Free Survival ◽

First Relapse ◽

Grade 3 ◽

One Year

Abstract Introduction: Combination therapy for longer periods but at low dose, also called metronomic scheduling, might be an effective manner to treat patients with relapsing myeloma. In particular if the used agents attack the malignant clone in an alternative manner. Therefore we used the combination of bortezomib, dexametasone and daily low dose of oral cyclophosphamide as an induction regimen followed by one year of maintenance therapy consisting of bortezomib and cyclophosphamide. Methods: Relapsing myeloma patients, bortezomib naïve, were treated with three cycles of 1.3 mg/m2 bortezomib at day 1, 4, 8 and 11, cyclophosphamide 50 mg daily, and 20 mg dexamethasone at day 1, 2, 4, 5, 8, 9, 11 and 12 followed by three cycles of bortezomib 1.6 mg/m2 (day 1, 8, 15 and 2), cyclophosphamide (50 mg) daily and dexamethasone (20 mg) at day 1, 2, 8, 9, 15, 16, 22 and 23. Maintenance therapy consisting of bortezomib 1.3 mg/m2 every two weeks and daily dose of 50 mg cyclophosphamide for one year was applied to patients in partial or complete remission. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression free and overall survival. Results: 59 patients with relapsing multiple myeloma were included of whom 69% were in first relapse (Table 1). The upfront treatment consisted mainly of thalidomide-based and vincristine-based chemotherapy and 40% of the patients have been treated with an autologous stem cell transplantation. All 6 cycles of induction chemotherapy could be given in 49% of the patients. Premature discontinuation before starting maintenance therapy was due to toxicity (31%), progressive disease (7%), death (7%) or other reasons (6%). Myelosuppression was the most common side effect with WHO grade 3-4 in 31% of the patients. Neuropathy grade 3-4 was observed in 16% of patients, partially due to the fact that bortezomib was given intravenously during the first 2 yrs of the protocol which included 76% of the patients. Maintenance therapy was started in 47% of the patients with a median duration of 7.3 months (range 0.36.-13.4). Grade 3-4 toxicity was observed in 25% of the patients including infections (n=3) and myelosuppression (n=3) which did not resulted in discontinuation of therapy. Median follow up time was 29 months with an overall response of 62%, and a very good partial response (VGPR), complete remission (CR) in 21% and 7% of the patients respectively. During the maintenance phase an improvement in responsiveness was observed in 25% of the patients. The CR rate increased with 9% to a total of 16%. VGPR rate was 20% and 16% of the patient had a PR. At end of the maintenance therapy 50% of patients started with maintenance had stable disease. The median progression free survival (PFS) was 17.2 months (range 0.13 – 43.5) as depicted in figure 1. and the median overall survival was 21.6 months (range 0.46-54.4, figure 2). During follow up 33 % of the patients died due to progression of MM. Conclusion: The present study demonstrates that combination therapy with bortezomib, continuous low dose cyclophosphamide and dexamethasone is an effective and manageable regimen. Adding a year of maintenance was feasible with limited side effects and an increase in CR rate. Table 1: patient characteristics Patients (%) Age, mean (min,max) 69 (46-86) Sex Male 56 Female 44 Relapse number First relapse 75 Second relapse 20 Third relapse 5 Performance status 0 65 1 29 2 5 M-protein heavy chain IgA 18 IgG 65 Light chain disease 18 Polyneuropathy No 61 Yes 39 Figure 1: Progression free survival Figure 1:. Progression free survival Figure 2: Overall survival Figure 2:. Overall survival Disclosures Waal de: Jansen Cilag: Research Funding. Munck de:Jansen Cilag: Research Funding. Woolthuis:Jansen Cilag: Research Funding. velden Van Der:Jansen Cilag: Research Funding. Tromp:Jansen Cilag: Research Funding. Hoogendoorn:Jansen Cilag: Research Funding. Vellenga:Jansen Cilag: Research Funding. Hovenga:Jansen Cilag: Research Funding.

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Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Lenalidomide and Dexamethasone (LD) for the Treatment of Non-Transplant Eligible Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.1845.1845 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1845-1845 ◽

Cited By ~ 4

Author(s):

Victor H Jimenez-Zepeda ◽

Christopher P. Venner ◽

Andrew Belch ◽

Irwindeep Sandhu ◽

Tatiana Nikitina ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Treatment Regimen ◽

Research Funding ◽

Clinical Characteristics ◽

Progression Free Survival ◽

Categorical Variables ◽

P Value ◽

Similar Response ◽

Free Survival

Abstract Introduction: Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. In the non-transplant eligible setting, recently a randomized controlled trial reported on the impact of Lenalidomide and Dexamethasone (LD), showing that this doublet-therapy is a feasible and efficacious combination. Based on the above-mentioned success of the LD combination, we aimed to compare the effect of CyBorD and LD for the treatment of non-transplant eligible MM (NTE) patients in the Alberta Myeloma and Dysproteinemia Program (AMDP). Patients and Methods: The primary objective was to assess ORR and PFS for NTE MM patients treated with CyBorD and LD. The recommended CyBorD regimen was as follows: bortezomib 1.3-1.5 mg/m2 SC or IV days 1, 8, 15 of a 28 day cycle (as of August, 2013 we adopted the a strategy whereby bortezomib can also be given on day 22), cyclophosphamide 300 mg/m2 PO days 1, 8, 15 and 22 and dexamethasone 20-40 mg PO days 1, 8, 15 and 22 with an aim to deliver a minimum of 9 cycles of treatment. LD was given at 25 mg days 1-21 of a 28-day cycle with Dexamethasone 20-40 mg PO days 1, 8, 15 and 22. Dose adjustments were at the discretion of the treating physician. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant and survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results: Ninety-one patients have received CyBorD and 56 have received LD. Clinical characteristics are shown in Table 1. At the time of analysis, 64 and 32 patients in the CyBorD and LD are alive of which 10 and 11, respectively, have progressed, ORR and VGPR rates were 85.7% and 56% for patients treated with CyBorD, and 83.9% and 64% for LD respectively (p=0.3). Estimated median OS was 40 months for CyBorD compared to 66 months for LD (p=0.156). In addition, median PFS was longer for LD patients compared to CyBorD (26 months vs 16.4 months, p=0.018). The rate of treatment discontinuation was similar between both groups (8.7% vs 10%, p=0.3). In Conclusion: CyBorD and LD appeared to be effective treatment options for NTE myeloma patients with similar response rates. Recognizing the limitations of a retrospective series, it is interesting to note a longer PFS and a trend towards better PFS in the LD group, however, longer follow-up and prospective validation is still required. Table 1. Clinical Characteristics Characteristic CyBorD, n=91 LD, n=56 P value Age (median) 73.9 73.6 0.2 GenderMaleFemale 57 (62.6%)34 (37.4%) 34 (60.7%)22 (39.3%) 0.8 B2microglobulin (µmol/L) 4.9 4.89 0.4 Albumin (g/L) 35 36 0.7 Stage IStage IIStage III 17.7%35.4%46.9% 23.5%37.2%39.3% 0.6 BMPC (%) 32 37.5 0.6 Heavy chain:IgGIgAFLC onlyIgDIgMBiclonal 501018113 26179010 0.068 Response rateORRCR/nCRVGPRPR 85.7%23%31.8%30.7 83.9%28%37.5%17.8% 0.3 Ab: BMPC: Bone marrow plasma cell Figure 1. Overall Survival according to treatment regimen Figure 1. Overall Survival according to treatment regimen Figure 2. Progression-Free survival according to treatment regimen Figure 2. Progression-Free survival according to treatment regimen Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; J&J: Honoraria. Venner:J&J: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria. Sandhu:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Duggan:Celgene: Honoraria; Jansen: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Research Funding; Amgen: Consultancy; Johnson & Johnson: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

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Sequential RCHOP, Radioimmunotherapy and Rituximab Maintenance Improves Early Outcomes in Advanced Stage Follicular Lymphoma: 5 Year Outcomes from SWOG 0801

Blood ◽

10.1182/blood.v128.22.614.614 ◽

2016 ◽

Vol 128 (22) ◽

pp. 614-614

Author(s):

Paul M. Barr ◽

Hongli Li ◽

Richard Burack ◽

Michael LeBlanc ◽

Sonali M. Smith ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Maintenance Therapy ◽

Follicular Lymphoma ◽

Research Funding ◽

Progression Free Survival ◽

Advanced Stage ◽

Secondary Malignancies ◽

Free Survival ◽

Grade 3

Abstract Background: Despite an abundance of effective therapeutic options, advanced stage follicular lymphoma (FL) remains incurable. Further, prospective trials consistently demonstrate that 20% of patients relapse within 2 years and ultimately have an inferior survival (Casulo 2015). Maintenace rituximab following chemoimmunotherapy induction is able to delay disease progression but has not demonstrated a benefit in overall survival (Salles 2011). Additionally, radioimmunotherapy (RIT) is one of the most effective single agent options in FL but is not commonly utilized as part of upfront treatment. As such, the role of both remains unclear. Based on results demonstrated with RIT consolidation in SWOG 0016 and the efficacy of rituximab maintenance, SWOG 0801 was designed as a phase 2 single arm trial, conducted to evaluate the utility of consolidative RIT and sequential maintenance rituximab following chemoimmunotherapy induction. Methods: Eligible patients (pts) with treatment naïve stage III/IV or bulky stage II FL received RCHOP for 6 cycles (without rituximab for the last 2 cycles) followed by iodine-131 tositumomab and subsequent rituximab administered every 3 months for up to 4 years. The primary endpoint was progression-free survival (PFS) at 3 years. Secondary endpoints included 5-year overall survival (OS), overall response rate (ORR), and safety. Results: Of 87 pts registered to this study, 85 were deemed eligible following central pathologic review. One additional patient withdrew consent and received no treatment on protocol. Of the 84 evaluable patients, the median age was 52 years (range 29 - 80) ) and 18%, 40%, and 42%had low, intermediate and high risk FLIPI scores, respectively. Seventy-three pts completed RCHOP and I-131 tositumomab. Grade ≥3 AEs occurring ≥5% of pts included neutropenia (57%), leukopenia (40%), thrombocytopenia (20%), febrile neutropenia (17%), fatigue (10%), neuropathy (8%), anemia (7%) and hyperglycemia (5%). Reasons for discontinuation included refusal of tositumumab (6 pts), prolonged myelosuppression (2 pts), ascites (1pt), inability to provide tositumumab (1 pt), and an unrelated lower extremity wound (1 pt). Following induction and RIT, 59 complete responses and 23 partial responses were observed, for a ORR of 99% (95% CI: 93.5%, 99.9%) Sixty nine eligible patients registered to maintenance therapy with 42 completing the 4 year treatment plan. The only grade ≥3 AE that occurred in ≥5% of pts was leukopenia (5%). Twenty-seven pts discontinued maintenance therapy, including 11 in the first 2 years and 16 in the last 2 years, due to the following reasons: infection (8 pts), patient preference (8 pts), deaths (2 pts), treatment delay (2 pts), secondary solid tumors (2 pts), bowel perforation (1 pt), joint pain (1 pt), hepatic transaminase elevation (1 pt), insurance refusal (1 pt), and dose error (1 pt). Four additional secondary malignancies were reported following completion of therapy including solid tumors (3 pts) and AML (1 pt). To date, 9 deaths have occurred due to secondary malignancies (3 pts), unknown etiology (3 pts), cardiac arrest (2 pts) and non-alcoholic cirrhosis (1 pt). After median follow-up of 5.6 years (range 3-7 years), 17 events have occurred including 9 pts experiencing progressive FL resulting in a progression free survival of 90% (95% CI: 81.9%, 95.1%) at 3 years and 84%(95% CI: 74.5%, 90.6%) at 5 years (Figure). Three-year overall survival is 96% (95% CI: 89.3%, 98.8%) and 5-year overall survival is 94% (95% CI: 86.2%, 97.5%). Conclusions: SWOG 0801 demonstrates near universal responses following chemoimmunotherapy and RIT. This sequential therapeutic strategy appears to improve early outcomes as 94% of pts are without disease progression at 2 years, consistent with the best results ever demonstrated for FL in the National Clinical Trials Network. However, the majority of discontinuations occurred during maintenance suggesting that rituximab over a 4-year span is not feasible for many patients due to cumulative toxicity. Future studies investigating precision strategies in high-risk FL may consider an aggressive chemoimmunotherapy induction and RIT consolidation platform to overcome early FL progression given these promising outcomes. Support: NIH/NCI grants CA180888, CA180819, and in part by GlaxoSmithKline. Figure. Progression-Free Survival and Overall Survival Figure. Progression-Free Survival and Overall Survival Disclosures Barr: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy. Smith:Amgen: Other: Educational lecture to sales force; Juno: Consultancy; Pharmacyclics: Consultancy; AbbVie: Consultancy; Portola: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Genentech: Consultancy, Other: on a DSMB for two trials ; TGTX: Consultancy. Gopal:Janssen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Consultancy. Persky:Merck: Research Funding; Gilead: Speakers Bureau. Press:Roche / Genentech: Consultancy, Research Funding. Fisher:Gilead: Consultancy; Seattle Genetics: Consultancy; Johnson and Johnson: Consultancy. Friedberg:Bayer: Other: Data Safety Monitoring Committee.

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Evaluation of Maintenance Therapy in Cutaneous T-Cell Lymphoma Patients Receiving Total Skin Electron Beam Radiation Therapy

Blood ◽

10.1182/blood-2018-99-111078 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1639-1639

Author(s):

Matthew Kudelka ◽

Mary Jo Lechowicz ◽

Mohammad K Khan ◽

Natia Esiashvili ◽

Christopher R Flowers ◽

...

Keyword(s):

Overall Survival ◽

Maintenance Therapy ◽

Median Time ◽

Research Funding ◽

Cell Lymphoma ◽

Progression Free Survival ◽

T Test ◽

Cutaneous T Cell Lymphoma ◽

Free Survival ◽

Time To First Treatment

Abstract Introduction: Total skin electron beam (TSEB) therapy is a well-established treatment modality for patients suffering from cutaneous T-cell lymphoma (CTCL). It is often augmented with maintenance therapy, including skin directed and systemic therapies. However, the utility of maintenance therapy remains controversial. We performed a retrospective analysis in patients with CTCL to assess whether maintenance therapy following TSEB improved outcomes. Methods: We conducted a single center retrospective analysis at the Winship Cancer Center of Emory University analyzing CTCL patients who received TSEB from 1998 - 2018. Patients who received TSEB were selected from an existing cutaneous lymphoma database, and cross referenced with a list of patients obtained from the Emory Cancer registry through the Lymphoid Malignancies Enterprise Architecture Database (LEAD) under an IRB-approved protocol. Consent was waived due to the retrospective nature of the project. The primary objective was to assess progression free survival in patients who received maintenance therapy following TSEB (PFS-TSEB) compared to those who did not. Maintenance therapy was defined as therapy started either concurrently or within 1 month of the initiation of TSEB. Secondary objectives were to assess overall survival following TSEB (OS-TSEB), and OS following diagnosis (OS). Additionally, we evaluated patient demographics, number of treatments, and time to TSEB from diagnosis. Equality of variances between groups was assessed with F-test. Numerical variables were analyzed with unpaired two-tailed t-tests or Welch's t-test and categorical variables were analyzed with chi-squared tests. Results: 101 patients with a median age of diagnosis of 55 years (range 10 - 89, 95% CI 52 - 58) underwent TSEB. 52% of patients were male, 48% female; 50% were black, 46% white/Hispanic, 65 % had MF, 16% SS, 16% CTCL NOS, 1% CD30+ CTCL, and 2% other. At diagnosis, 33% were stage 1, 39% stage 2, 10% stage 3, and 18% stage 4. 48% of patients received maintenance treatment and 52% did not; 36% of maintenance was given concurrently with TSEB, 34% after, and 30% unknown. The most common maintenance therapies were bexarotene (29%), interferon (23%), and PUVA (15%). From diagnosis, median time to first treatment was 48 days (IQR 11 - 152), time to TSEB was 429 days (IQR 136 - 1225), and median time to first treatment after TSEB was 51 days (IQR 18 - 115). A median of 2 therapies were received prior to TSEB (IQR 1 - 4; 1 skin-directed, 1 systemic, 0 RT). A median of 2 therapies occurred following TSEB (IQR 0 - 4.5; 0 skin-directed, 1 systemic, 0 RT). The most common skin directed and systemic treatments overall were topical steroids (pre, post-TSEB), PUVA (pre-TSEB), and retinoids (post-TSEB). Overall, 80% of patients progressed after TSEB with a median time to progression of 118 days (IQR 36.5 - 231.5). OS-TSEB and OS were 642.5 d (IQR 248 - 1587.5) and 1523 (IQR 785 - 2698), respectively, with 46% of patients alive and 54% dead. In comparing outcomes of maintenance to no maintenance, PFS-TSEB was 171 days (IQR 30.25 - 333.75) versus 66.5 days (IQR 30 - 178.75) (Welch's t-test, P = .067), OS-TSEB was 1135 days (IQR 476.5 - 1845.5) versus 433.5 (IQR 219 - 1309.75) (t-test, P = .046), and OS was 1871 (IQR 961 - 2698) versus 1329.5 days (IQR 676.5 - 2830.75) (t-test, P = 0.74), respectively. We found no difference in gender, race, diagnosis, stage, or age at diagnosis between maintenance and no maintenance groups. However, in comparing maintenance to no maintenance, time to initiate TSEB from diagnosis was shorter in the maintenance group (322 days [109.5 - 772] versus 456 days [IQR 152 - 1784]) (t-test, P = 0.041). Median total number of treatments was 8 (IQR 4 - 10) versus 5 (IQR 3-9) (t-test, P = 0.052), respectively. Conclusion: We defined demographics, diagnoses, stage, treatment number, treatment type, and outcomes in a cohort of CTCL patients undergoing TSEB. Patients receiving maintenance therapy had an increase in overall survival and a trend towards an increase in progression-free survival measured after TSEB. A possible limitation to these findings is that patients receiving maintenance therapy in our cohort received TSEB earlier than those without maintenance, with a trend towards more overall treatments. Our retrospective findings suggest a benefit of maintenance therapy in CTCL following TSEB and provide a basis for initiating prospective studies to further evaluate this approach. Disclosures Flowers: Gilead: Research Funding; Burroughs Wellcome Fund: Research Funding; Abbvie: Consultancy, Research Funding; Pharmacyclics: Research Funding; Gilead: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech/Roche: Consultancy; BeiGene: Research Funding; Janssen Pharmaceutical: Research Funding; Pharmacyclics/ Janssen: Consultancy; Spectrum: Consultancy; Karyopharm: Consultancy; Abbvie: Research Funding; Genentech/Roche: Research Funding; OptumRx: Consultancy; Millennium/Takeda: Research Funding; Celgene: Research Funding; Denovo Biopharma: Consultancy; TG Therapeutics: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding. Allen:Merck: Research Funding; Bayer: Consultancy.

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Maintenance Rituximab Is Associated with Improved Progression Free and Overall Survival in Waldenstrom's Macroglobulinemia.

Blood ◽

10.1182/blood.v114.22.3750.3750 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3750-3750

Author(s):

Steven P Treon ◽

Christina Hanzis ◽

Robert Manning ◽

Thea Ioakimidis ◽

Christopher J Patterson ◽

...

Keyword(s):

Overall Survival ◽

Maintenance Therapy ◽

Induction Therapy ◽

Nucleoside Analogue ◽

Research Funding ◽

Progression Free Survival ◽

Median Number ◽

Free Survival ◽

Categorical Response ◽

Waldenström's Macroglobulinemia

Abstract Abstract 3750 Poster Board III-686 Rituximab is an important mainstay of therapy in patients with Waldenstrom's macroglobulinemia, though the benefit of maintenance rituximab has not been established. As such, we examined the outcome of patients followed at our Institution who responded to a rituximab based therapy, and assessed the impact of maintenance rituximab. Two hundred forty eight patients were included in this analysis, of whom 86 (35%) received maintenance rituximab following response. No difference in baseline age, serum IgM, IgA, IgG, BM disease involvement, complete blood counts, B2M levels, as well as categorical response rates (CR, VGPR, PR and MR) following induction therapy were observed between cohorts. 181 (73%) patients were previously untreated, with a similar proportion in both cohorts. Induction therapy for all patients included rituximab alone (n=79), or in combination with bortezomib (n=40); cyclophosphamide (n=44); immunomodulatory agent (n=31); or a nucleoside analogue (n=54) containing regimen. The median number of rituximab infusions given as induction was 6 for both cohorts, while the median number of rituximab infusions given as maintenance was 8. Maintenance rituximab was administered as 1 infusion (at 375 mg/m2) every 3 months for 63 (73%) patients, and as 4 weekly infusions (at 375 mg/m2) every 6 months for 23 (27%) patients, with a median of 2 years of treatment. Both progression free (56.3 vs. 28.6 months; p=0.0001) and overall survival (>120 vs. 116 months; p=0.0095) were longer in those patients who received maintenance rituximab (Figs. A, B). Improved progression free survival was evident despite previous untreated or treated status, induction with rituximab alone or in combination therapy, as well as induction with a cyclophosphamide, nucleoside analogue or bortezomib containing regimen (p=0.0001). Among patients receiving maintenance rituximab, progression free survival was 53.3 versus 61.3 months (p=0.4931) for those patients receiving one infusion of rituximab every three months compared to those receiving 4 weekly infusions every 6 months, respectively. Best response serum IgM was 598 vs. 1380 mg/dL (p<0.0001), and hematocrit was 40.7% vs. 38.6% (p=0.001) in patients who received maintenance versus no maintenance, respectively. Categorical response improvement was also observed in 33/86 (38.4%) patients following maintenance therapy. Among patients receiving maintenance therapy, median serum IgG (351 vs. 461 mg/dL; p=0.0008) and IgA (23 vs. 33 mg/dL; p=0.09) levels were lower, and an increased number of infectious events during the course of follow-up were observed (p=0.008) which were mainly sinopulmonary though ≤grade 2. The results support the use of maintenance rituximab in WM patients who respond to induction with a rituximab containing regimen, and highlight the need for further studies aimed at clarifying the ideal schedule and duration of maintenance rituximab therapy in WM. Disclosures: Treon: Genentech BioOncology Inc.: Consultancy, Honoraria, Research Funding; Biogen IDEC Inc.: Consultancy, Honoraria, Research Funding.

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A Case Control Study of Syngeneic Transplantation Versus Autologous Transplantation for Multiple Myeloma: Two Decades of Experience at MD Anderson

Blood ◽

10.1182/blood.v128.22.4613.4613 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4613-4613

Author(s):

Ghulam Rehman Mohyuddin ◽

Muhammad Salman Faisal ◽

Nina Shah ◽

Qaiser Bashir ◽

Chitra Hosing ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Research Funding ◽

Plasma Cells ◽

Progression Free Survival ◽

Disease Status ◽

Free Survival ◽

First Remission ◽

Equity Ownership ◽

Relapsed Disease

Abstract INTRODUCTION: High-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) is the standard of care for eligible patients with newly diagnosed multiple myeloma. However, almost all patients eventually relapse possibly due to incomplete elimination of malignant plasma cells. For patients with an identical twin, syngeneic-HCT provides a tumor-free graft without the risk of graft vs. host disease. We hypothesized that syngeneic-HCT would result in better disease control than auto-HCT. METHODS : We identified 10 patients with multiple myeloma who underwent syngeneic-HCT at our institution from 1994 to 2014. Using a propensity score, we identified 48 controls that received auto-HCT during the same time interval. Matching was done for the year of transplant, age and disease status at auto-HCT (Table 1). Primary endpoint was progression-free survival (PFS). Secondary endpoints were complete remission (CR) rates and overall survival (OS). RESULTS: Baseline characteristics are shown in Table 1. The two groups were well matched, with no significant statistical differences in age, sex, race, stage at diagnosis, lines of therapy received, or disease status prior to transplant. At the time of transplant, 7 (70%) patients in the syngeneic cohort were in first remission, with 3 (30%) having relapsed disease. Similarly, 28 (58%) patients in the autologous cohort were in first remission, with 20 (41%) having relapsed disease (p value 0.49). Patient outcomes are summarized in Table 2. All patients engrafted, with a median time to engraftment of 11 and 10 days, for the syngeneic and auto-HCT cohorts respectively (p=0.22). There was no treatment related mortality in the first 100 days post-transplant in either of the cohorts. In the syngeneic group 8 (80%) patients achieved ≥ CR, 1 achieved very good partial remission (VGPR), and 1 achieved a partial remission (PR), with an overall response rate (ORR) of 100%. Amongst the control group, 18 (37%) achieved ≥ CR, 5 (10%) achieved ≥ VGPR, 21 (43%) achieved ≥PR, 3 (6%) had stable disease and 1 (2%) had disease progression, with an ORR of 91.6%. There was no significant difference in the ORR between the two groups (p=0.21). At the time of last follow-up, a total of 4 (40%) patients had relapsed in the syngeneic cohort, and 31 (65%) had relapsed in the autologous cohort (p=0.15). The median progression free survival (PFS) for the syngeneic cohort was 98.6 months (95% CI from 76-118 months), while the median PFS for auto-HCT cohort was 34.5 months (95% CI from 16-52 months) (p=0.05). Median overall survival (OS) for the syngeneic and auto-HCT cohorts were not reached and 131 months, respectively (p=0.15). The PFS difference was not due to a difference in maintenance therapy after transplant, as 6 (60%) syngeneic patients and 32 (66.7%) auto-HCT (p=0.69) received maintenance therapy respectively. CONCLUSION: Our study shows that patients with multiple myeloma who underwent syngeneic-HCT had a trend to a higher CR rate and longer PFS compared to a matched cohort that underwent auto-HCT. This benefit may be related to the absence of malignant plasma cells in the syngeneic graft, and a normal donor immune system. The efficacy of syngeneic transplants needs to be assessed in a larger number of patients to provide sufficient power to detect clinically meaningful differences with autologous transplants. Table 1 Pre-transplant variables for cases and controls. Table 1. Pre-transplant variables for cases and controls. Table 2 Transplant Outcomes Table 2. Transplant Outcomes Kaplan Maier Curves for Progression Free Survival and Overall Survival. Kaplan Maier Curves for Progression Free Survival and Overall Survival. Disclosures Bashir: Takeda: Consultancy; Spectrum: Consultancy; Takeda: Research Funding; Celgene: Research Funding. Champlin:Ziopharm Oncology: Equity Ownership, Patents & Royalties; Intrexon: Equity Ownership, Patents & Royalties.

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Efficacy and prognostic significance of triflurodine/tipiracil beyond oxaliplatin and irinotecan based chemotherapy in patients with refractory metastatic colorectal cancer: An observational multicenter study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15586 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15586-e15586

Author(s):

Mohamed Alghamdi ◽

Shouki Bazarbashi ◽

Elsamany Shereef ◽

Mervat Mahrous ◽

Omar Al shaer ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Saudi Arabia ◽

Neutrophil Count ◽

Prognostic Significance ◽

Progression Free Survival ◽

P Value ◽

Second Line ◽

First Line ◽

Free Survival

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

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Patterns of Care and Treatment Pathways for Non-Surgically Managed Early and Locally Advanced Non-Small Cell Lung Cancer Patients at Ain Shams University Clinical Oncology Department: a Retrospective and Descriptive Analysis

QJM ◽

10.1093/qjmed/hcab103.006 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Dr/Khaled Abdel Karim ◽

Dr/Khaled Nagib ◽

Dr/Ahmed Hassan Abd El Aziz ◽

Christina Gamil Garas

Keyword(s):

Overall Survival ◽

Clinical Oncology ◽

Locally Advanced ◽

Progression Free Survival ◽

Patterns Of Care ◽

P Value ◽

Treatment Pathways ◽

Free Survival ◽

Care And Treatment ◽

Nsclc Patients

Abstract Background Lung cancer is the leading cause of cancer death worldwide, but little is known about how patients with this disease are managed. Aim of the Work We aim to study patterns of care and treatment pathways of non- surgically managed early and locally advanced NSCLC patients from January 2015 to December 2018 in Ain Shams University Clinical Oncology Department. Patients and Methods In this retrospective analysis we included patients the met the following criteria; age >18, histologically confirmed NSCLC patients whom didn’t undergo surgical resection with at least 6 months of follow up data. We collected data from Clinical Oncology department archive in Ain Shams university hospital. Our primary objective is to identify the patterns of care and treatment pathway for non surgically managed NSCLC patients in ASUCOD from January 2015 to December 2018. Results 86 patients finally met our inclusion criteria. Median age at diagnosis of 61 years with a range of (38-85), 95.3% were male. Most of the patients were stage III; 40.7% were stage IIIA, 41.9% were stage IIIB, and 9.3% were stage IIIC. 41 were treated radically, 37 received palliative treatment and only 8 patients received supportive care. Overall median progression free survival in our patients was 9.23 (7.4-13.5) and overall survival duration was13.4 (9.5-18.0). In radically treated patients, 68.3% received sequential chemoradiotherapy (sCRT), 29.2% received concurrent chemoradiotherapy (cCRT) or 2.4% received definitive radiotherapy alone (RT). In palliative treated patients, 73% received chemotherapy alone (CTX), 8.1% received palliative RT and 18.9% received both chemotherapy and palliative dose of radiotherapy (CRT). All treatment modalities were similar regarding median progression free survival and overall survival durations, 17.5 (3.6–19.6) and 20.6 (3.6–31.6) in cCRT, 17.5 (3.6–19.6) and 23.3 (17.7–31.2) in sCRT, 12.9 and 13.4 RT group, P value=0.57 and 0.16 receptively. Similarly, progression free survival and overall survival durations were 8.8 (3.0–15.8) and 16.2 (3.6–18.7) in CRT, 5.3 (0.4–7.6) and 8.6 (6.2–10.2) in CTX, 8.5 (0.4–8.5) and 8.5 (0.4–8.5) in palliative RT group, P value=0.64 and 0.15 receptively. In our study, first-line chemotherapy were Gemcitabine plus Cisplatin (41.9%) or Carboplatin (35.1%).The Second -line chemotherapy were Docetaxel (63.1%) or Paclitaxel plus Carboplatin (26.3%). Paclitaxel plus Carboplatin were the most regimen given with RT. Most of the patients received radiation dose of 60Gy/30Fr (73.2%). Regarding the incidence of toxicity, there were significant high rates of esophagitis in cCRT in grade 3 or more compared to sCRT. Conclusion We have found that less than half of this study population were treated radically while the other half received palliative treatment. And only few patients received best supportive care. Radically treated patients had higher progression free survival and overall survival durations compared to palliative and supportive treatment.

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Prognostic factors for patients treated with abiraterone

Future Science OA ◽

10.2144/fsoa-2019-0079 ◽

2020 ◽

Vol 6 (2) ◽

pp. FSO436 ◽

Cited By ~ 2

Author(s):

Cecília M Alvim ◽

André Mansinho ◽

Rita S Paiva ◽

Raquel Brás ◽

Patrícia M Semedo ◽

...

Keyword(s):

Overall Survival ◽

Median Overall Survival ◽

Specific Antigen ◽

Progression Free Survival ◽

Abiraterone Acetate ◽

Hazard Ratio ◽

Castration Resistant Prostate Cancer ◽

Free Survival ◽

Castration Resistant ◽

Prognostic And Predictive Factors

Aim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10−0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14−0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.

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Does endometriosis have an effect on the survival of women with synchronous endometrial and ovarian cancer?

Journal of Endometriosis and Pelvic Pain Disorders ◽

10.1177/2284026519893537 ◽

2019 ◽

Vol 11 (4) ◽

pp. 185-193

Author(s):

Engin Celik ◽

Hale Goksever Celik ◽

Hamdullah Sozen ◽

Semen Onder ◽

Merve Baktiroglu ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Confidence Interval ◽

Detrimental Effect ◽

Clear Cell ◽

Cell Cancer ◽

Progression Free Survival ◽

Hazard Ratio ◽

Free Survival ◽

Pathological Characteristics

Purpose: Synchronous endometrial and ovarian cancer is defined as the concurrent presence of ovarian cancer with endometrial cancer. We aimed to evaluate whether there is an effect of endometriosis on progression-free survival and overall survival of women with synchronous endometrial and ovarian cancer. We also compared these findings with the patients having endometrial-only tumors and ovarian-only tumors. Methods: The patients who underwent surgery for endometrioid or clear-cell endometrial-only tumors and/or ovarian-only tumors and synchronous endometrial and ovarian cancer between 2005 and 2016 were included in this cohort study. The effect of the presence of endometriosis on progression-free survival and overall survival in these women who met the criteria was determined using statistical methods. Women were also compared regarding their demographic, clinical, and pathological characteristics. Results: A total of 176 patients were included in this study. All histology types of tumors located in endometrium or ovary were endometrioid or clear-cell cancer. Endometriosis was present in 62 patients (35.2%), whereas adenomyosis was present in 44 patients (25%). Endometriosis was diagnosed more frequently in women with ovarian-only tumors and synchronous endometrial and ovarian cancer than those with endometrial-only tumors (59.2% vs 5.7%, p < 0.001 and 45.7% vs 5.7%, p < 0.001, respectively). The patients with endometriosis showed no significantly longer progression-free survival and overall survival (hazard ratio = 1.70; 95% confidence interval = 0.48–6.03; p = 0.408 and hazard ratio = 1.67; 95% confidence interval = 0.30–9.44; p = 0.562, respectively). The presence of endometriosis was a stronger predictor for progression-free survival and overall survival comparing with the presence of adenomyosis. Conclusion: The women with synchronous endometrial and ovarian cancer should be informed that endometriosis has no detrimental effect on progression-free survival and overall survival.

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