Oncogenic Targets, Magnitude of Benefit, and Market Pricing of Antineoplastic Drugs

Purpose The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported. Patients and Methods Randomized clinical trials (RCTs) that evaluated approved new agents for solid tumors by the US Food and Drug administration since the year 2000 were assessed. Hazard ratios (HRs) and 95% CIs were extracted for time-to-event end points described for each RCT. HRs were pooled for three groups: agents directed against a specific molecular target, for which the target population is selected by a biomarker (group A); less specific biologic targeted agents (group B); and chemotherapeutic agents (group C). Monthly market prices of these different drugs were compared. Results For overall survival (OS), the pooled HR was 0.69 (95% CI, 0.59 to 0.81) for group A (six drugs, six trials); it was 0.78 (95% CI, 0.74 to 0.83) for group B (seven drugs, 14 trials); and it was 0.84 (95% CI, 0.79 to 0.90) for group C (eight drugs, 12 trials). For progression-free survival (PFS), the pooled HR was 0.42 (95% CI, 0.36 to 0.49) for group A (six drugs, seven trials); it was 0.57 (95% CI, 0.51 to 0.64) for group B (seven drugs, 14 trials); and it was 0.75 (95% CI, 0.66 to 0.85) for group C (six drugs, 10 trials). Tests for heterogeneity between subgroups were highly significant for PFS (P < .001) and OS (P = .02). The median monthly prices for standard doses of drugs were $5,375 for group A, $5,644 for group B, and $6,584 for group C (P = .87). Conclusion New agents with specific molecular targets are clinically the most beneficial, but their monthly market prices are not significantly different from those of other anticancer agents.

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Randomized trial of medical compression stockings versus two-layer short-stretch bandaging in the management of venous leg ulcers

Phlebologie ◽

10.1055/s-0037-1622268 ◽

2009 ◽

Vol 38 (04) ◽

pp. 157-163 ◽

Cited By ~ 9

Author(s):

A. Franek ◽

L. Brzezinska-Wcislo ◽

E. Blaszczak ◽

A. Polak ◽

J. Taradaj

Keyword(s):

Drug Therapy ◽

Randomized Clinical Trials ◽

Therapy Group ◽

Long Term Results ◽

Leg Ulcers ◽

Compression Stockings ◽

Venous Leg Ulcers ◽

Group A ◽

Group B ◽

Medical Compression Stockings

SummaryA prospective randomized clinical trial was undertaken to compare a medical compression stockings with two-layer short-stretch bandaging in the management of venous leg ulcers. Study endpoints were number of completely healed wounds and the clinical parameters predicting the outcome. Patients, methods: Eighty patients with venous leg ulcers were included in this study, and ultimately allocated into two comparative groups. Group A consisted of 40 patients (25 women, 15 men). They were treated with the compression stockings (25–32 mmHg) and drug therapy. Group B consisted of 40 patients (22 women, 18 men). They were treated with the short-stretch bandages (30–40 mmHg) and drug therapy, administered identically as in group A. Results: Within two months the 15/40 (37.50%) patients in group A and 5/40 (12.50%) in group B were healed completely (p = 0.01). For patients with isolated superficial reflux, the healing rates at two months were 45.45% (10/22 healed) in group A and 18.18% (4/22 healed) in group B (p = 0.01). For patients with superficial plus deep reflux, the healing rates were 27.77% (5/18 healed) in group A and 5.55% (1/18 healed) in group B (p = 0.002). Comparison of relative change of the total surface area (61.55% in group A vs. 23.66% in group B), length (41.67% in group A vs. 27.99% in group B), width (46.16% in group A vs. 29.33% in group B), and volume (82.03% in group A vs. 40.01% in group B) demonstrated difference (p = 0.002 in all comparisons) in favour of group A. Conclusion: The medical compression stockings are extremely useful therapy in enhancement of venous leg ulcer healing (both for patients with superficial and for patients who had superficial plus deep reflux). Bandages are less effective (especially for patients with superficial plus deep reflux, where the efficiency compared to the stockings of applied compression appeared dramatically low). These findings require confirmation in other randomized clinical trials with long term results.

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Chemioprofilassi endovescicale del carcinoma uroteliale superficiale. Studio su mitomicina ed epirubicina in differenti dosaggi

Urologia Journal ◽

10.1177/039156039406101s06 ◽

1994 ◽

Vol 61 (1_suppl) ◽

pp. 25-29

Author(s):

M. Pastorello ◽

A. Molon ◽

M. Poluzzi ◽

F. Venturi ◽

I. Siggillino

Keyword(s):

Recurrence Rate ◽

Tumour Progression ◽

Transitional Cell ◽

Chemotherapeutic Agents ◽

High Recurrence Rate ◽

Multiple Neoplasms ◽

Group A ◽

Group B ◽

Histological Confirmation

Superficial transitional cell carcinomas (TCC) of the bladder have a high recurrence rate and a potential for progressive disease. The intravesical use of chemotherapeutic agents to prevent recurrences has achieved varying success. We report our experience in the prevention of superficial TCC recurrences using topical Mitomycin C or Epirubicin (in two different doses). After complete transurethral resection (TURB) and histological confirmation of stage pTa or pT1 disease, 80 patients were assigned to group A (Mitomycin 40 mg in 40 ml); 80 pts to group B (Epirubicin 50 mg in 50 ml); 40 pts were enrolled in group C (Epirubicin 80 mg in 50 ml saline). Median follow-up is 43.4 months for group A, 42.1 months for gr. B, 21.1 months for gr. C. 183 pts could be evaluated. Results: 28/74 pts had recurrences in gr. A, 26/73 in gr. B, 11/36 in gr. C; the recurrence index/100 pt-months is 1.21 in gr. A, 1.23 in gr. B, 2.10 in gr. C. Tumour progression was registered in 13/74 pts in gr. A, in 11/73 in gr. B, in 5/36 in gr. C. pT1-tumours showed a recurrence rate of 69% (average of the three groups) versus 13% of pTa-tumours; a very high recurrence rate was also observed in multiple neoplasms.

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Cisplatin, Cetuximab, and Radiation in Locally Advanced Head and Neck Squamous Cell Cancer: A Retrospective Review

Clinical Medicine Insights Oncology ◽

10.4137/cmo.s18682 ◽

2015 ◽

Vol 9 ◽

pp. CMO.S18682 ◽

Cited By ~ 14

Author(s):

Prakash Peddi ◽

Runhua Shi ◽

Binu Nair ◽

Fred Ampil ◽

Glenn M. Mills ◽

...

Keyword(s):

Head And Neck ◽

Performance Status ◽

Cell Cancer ◽

Locally Advanced ◽

Progression Free Survival ◽

Rank Test ◽

Advanced Head ◽

Significant Difference ◽

Group A ◽

Group B

Efficacy of cisplatin versus cetuximab with radiation in locally advanced head and neck cancer (LAHNC) was evaluated. A total of 96 patients with newly diagnosed LAHNC treated at our institution between 2006 and 2011 with concurrent radiation and cisplatin (group A, n = 45), cetuximab (group B, n = 24), or started with cisplatin but switched to cetuximab because of toxicity (group C, n = 27) were reviewed. Chi-square test, analysis of variance, and log-rank test were used for analysis. The three groups had similar baseline characteristics, except for median age, T stage, albumin levels, hemoglobin levels, performance status, and comorbidities. A complete response (CR) was seen in 77%, 17%, and 67% of patients ( P < 0.001), respectively. There was no significant difference in median overall survival (OS) between groups A and C. The median OS for groups A and C was not reached (>65 months), even though it was significantly longer than median OS for group B (11.6 months; P ≤ 0.001). The 2-year OS in groups A and C is significantly higher than that in group B (70% for groups A and C, 22% for group B). There is no significant difference in progression-free survival (PFS) between groups A and C. The median PFS for these groups was not reached (>62 months), and is significantly longer than that for group B (4.3 months; P ≤ 0.001). The 2-year PFS of group A (67%) and group C (76%) was significantly longer than that of group B (20%). Cisplatin with radiation appears to be more efficacious even in suboptimal dosing than cetuximab with radiation in LAHNC but the two groups were not well matched.

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Thalidomide Based Regimens (TBR) for Relapsed/Refractory Multiple Myeloma Patients: Long Term Follow Up, Unmaintained Remissions and Disease Control after Subsequent Treatments.

Blood ◽

10.1182/blood.v110.11.4812.4812 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4812-4812

Author(s):

Maria Roussou ◽

Efstathios Kastritis ◽

Athanasios Anagnostopoulos ◽

Evangelos Eleftherakis-Papaiakovou ◽

Charis Matsouka ◽

...

Keyword(s):

Multiple Myeloma ◽

Progression Free Survival ◽

Free Survival ◽

Refractory Multiple Myeloma ◽

Long Term Follow Up ◽

Group A ◽

Pulse Dexamethasone ◽

Group B

Abstract Introduction: The effectiveness of thalidomide based regimens (TBR) in patients with relapsed/refractory multiple myeloma is well established. However, there are still limited data regarding the long term follow up after such regimens and the outcome of patients when they progress and they receive further treatment. In order to answer these questions we evaluated a series of 114 patients with relapsed/refractory multiple myeloma who were treated with TBR. None of these patients had previously received thalidomide, bortezomib or lenalidomide. Patients and Methods: All patients were treated with thalidomide and dexamethasone with or without other oral agents. More specifically 41 patients had received continuous thalidomide and pulse dexamethasone, 25 patients clarithromycin, continuous thalidomide and pulse dexamethasone, 43 patients intermittent thalidomide, pulse dexamethasone and cyclophosphamide and 5 patients continuous thalidomide, pulse dexamethasone and cyclophosphamide. Type of treatment at the time of progression after TBR, response to this treatment and progression free survival were recorded for each patient. Moreover, patients who received novel agents after progression to TBR, were divided into 2 subgroups, according to their resistance to thalidomide. In group A, patients had refractory or progressive myeloma while on TBR or within 2 months after discontinuation of TBR. In group B, myeloma progressed more than 2 months after discontinuation of TBR. Results: Among the 114 patients, 41 had not responded to TBR and 73 (64%) had achieved at least a partial response. The median PFS for all patients was 8 months. As of June 2007, 10 patients remain without progression from 28 to 81 months (median 54 months). Eight patients remain off treatment and without progression for a median of 56 months (range 28–81). Patients who did not respond to or progressed after TBR were analyzed for further treatment and outcome. Thirty eight patients (37%) died before receiving further treatment, 23 patients (23%) received conventional chemotherapy and 41 patients (40%) received continuous thalidomide and dexamethasone +/− clarithromycin or cyclophosphamide (17 patients), bortezomib and dexamethasone (7 patients), melphalan-bortezomib-dexamethasone and intermittent thalidomide (12 patients) or lenalidomide with dexamethasone (5 patients). Among these 41 patients, 24 were classified in group A (thalidomide resistant) and 17 in group B. Overall 17 (41%) achieved at least partial response after retreatment with novel agent-based regimens. A response was observed in 46% of patients in group A and in 35% of patients in group B. The median progression free survival of the 41 patients who received retreatment with novel agents was 9.2 months and the median survival was 17 months. Among the 23 patients who received conventional chemotherapy only five (21%) patients responded and the progression free survival and the median survival were 5.3 and 10.2 months, respectively. Conclusions: After an oral TBR regimen 6 (5%) patients remain without treatment and free of progression for more than 4 years. A significant number of patients who progressed after TBR and who received further treatment which included a novel agent achieved a response, including several patients who were resistant to TBR.

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Retrospective analysis of first-line chemotherapy in 132 patients with advanced small-bowel adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.260 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 260-260

Author(s):

T. Tsushima ◽

N. Boku ◽

Y. Honma ◽

H. Takahashi ◽

S. Ueda ◽

...

Keyword(s):

Small Bowel ◽

Univariate Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Ampullary Carcinoma ◽

Small Bowel Adenocarcinoma ◽

Kaplan Meier ◽

Group A ◽

Group B ◽

Ecog Ps

260 Background: No standard care has been established for advanced small-bowel adenocarcinoma (SBA). The aim of this study is to explore a most promising chemotherapy regimen for advanced SBA. Methods: All data were collected from medical records of patients with advanced or recurrent SBA who received chemotherapy between April 1999 and March 2009 at 41 hospitals in Japan. Selection criteria were as follows: 1) histologically proven SBA, excluding ampullary carcinoma, 2) no previous chemotherapy or radiotherapy, 3) ECOG PS 0-2, 4) adequate bone marrow, hepatic and renal functions, 5) no concomitant malignancy. Patients were divided into the five groups by regimens: group A, fluoropyrimidine alone; group B, fluoropyrimidine + cisplatin; group C, fluoropyrimidine + oxaliplatin; group D, fluoropyrimidine + irinotecan; group E, others. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Results: Demographics of selected 132 patients were: median age (range), 59 (23-78) years; male/female, 87/45; location of primary tumor, duodenum/jejunum/ileum/unknown, 80/32/17/3; advanced/recurrent disease, 91/41. The numbers of the patients in group A, B, C, D and E were 60, 17, 22, 11 and 22, and objective response rates (ORR) in the patients with target lesions were 20% (9/46), 38% (5/13), 42% (8/19), 25% (2/8), 21% (4/19), respectively. Median PFS and OS were 6.0 and 14.0 months for the whole population, and those in each group are shown in the Table.In comparison with fluoropyrimidine alone (A), oxaliplatin-combined regimens (C) associated with better PFS (HR=0.53 [0.31-0.93], p=0.03) and OS (HR=0.64 [0.33-1.25], p=0.19), while cisplatin-combined regimens (B) did not (HR=1.54 [0.88-2.68], p=0.13 for PFS and HR=1.67 [0.94-2.97], p=0.08 for OS) by univariate analysis. Conclusions: It is suggested that oxaliplatin-combined regimens might be the most promising regimen for advanced SBA. [Table: see text] No significant financial relationships to disclose.

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Randomized phase III study comparing FOLFOX + bevacizumab versus folfoxiri + bevacizumab (BEV) as 1st line treatment in patients with metastatic colorectal cancer (mCRC) with ≥3 baseline circulating tumor cells (bCTCs).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3507 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3507-3507 ◽

Cited By ~ 8

Author(s):

Javier Sastre ◽

Jose María Vieitez ◽

Maria Auxilidora Gomez-España ◽

Silvia Gil Calle ◽

Antonieta Salud Salvia ◽

...

Keyword(s):

Primary Endpoint ◽

Progression Free Survival ◽

Phase Iii ◽

Adequate Treatment ◽

Poor Prognostic Factor ◽

Efficacy Analysis ◽

Secondary Endpoints ◽

Group A ◽

Phase Iii Study ◽

Group B

3507 Background: FOLFOXIRI+BEV has demonstrated a survival benefit compared with FOLFIRI plus BEV (TRIBE Lancet Oncol 2015) in first-line mCRC. Nevertheless, due to its safety profile, this schedule is not recommended for all pts. In addition, we have showed that the detection of ≥3 bCTCs is a poor prognostic factor for survival (MACRO The Oncologist 2012). The VISNU-1 trial compares FOLFOX + BEV vs FOLFOXIRI + BEV in pts with mCRC and ≥3 bCTCs. Progression-free survival (PFS) is the primary endpoint. Secondary endpoints included overall response rate (ORR) and overall survival (OS). Methods: This is an open, multicentric, randomized phase III trial. Patients with mCRC younger than 70 years, ECOG 0-1 were randomized to FOLFOX+BEV (arm A) or FOLFOXIRI+BEV (arm B), stratified per KRAS mutation (mutated vs WT) and number of involved organs (1 vs >1). Results: 349 pts were included in the ITT population; 177 in group A and 172 in group B. Characteristics of the pts, molecular profiling and safety analysis have been previously presented at ASCO 2018 and showed that this schedule had an acceptable toxicity profile. Efficacy analysis in the ITT population is shown in the table. Conclusions: In this population with very bad prognosis, our study met its primary endpoint. Pts who received FOLFOXIRI + Bev benefit for a statistically significative PFS and ORR. OS showed a trend of benefit in the experimental arm. According to these results, FOLFOXIRI-Bev could be considered an adequate treatment option for pts with mCRC and ≥3 bCTCs. Clinical trial information: 2012-000846-37. [Table: see text]

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Efficacy and safety of FOLFIRINOX in elderly patients with advanced pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15729 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15729-e15729

Author(s):

Jae Hyup Jung ◽

Jingu Kang ◽

Jong-Chan Lee ◽

Jin-Hyeok Hwang

Keyword(s):

Elderly Patients ◽

Performance Status ◽

Locally Advanced ◽

Progression Free Survival ◽

Elderly Group ◽

Ductal Adenocarcinoma ◽

First Line ◽

Tertiary Teaching ◽

Group A ◽

Group B

e15729 Background: Although FOLFIRINOX showed improved efficacy in advanced pancreatic ductal adenocarcinoma (PDA), physicians still hesitate to administrate FOLFIRINOX in elderly patients despite of being in a good performance status. We investigated the efficacy and toxicity of FOLFIRINOX in elderly patients with advanced PDA. Methods: We retrospectively reviewed electronic medical records of advanced PDA patients administrated a first-line FOLFIRINOX from January 2012 to July 2017 in a single tertiary teaching hospital. All the patients were divided into two groups: non-elderly group A (age < 70) and elderly group B (age≥70). Overall survival (OS), progression free survival (PFS) and toxicities were compared between two groups using Cox proportional hazard model. Results: A total of 214 patients (Group A 176; B 38) met the eligible criteria. Median age was 61 years old (29-80, group A 59; B 73) and median cycle of FOLFIRINOX was 7.0 (1–75, group A and B 7.0). Median OS and PFS did not differ between group A and B (OS, 11.8 vs 12.0 months, hazard ratio [HR] 1.165, 95% confidence interval [CI] 0.785–1.728; PFS 6.5 vs 7.3 months, HR 1.003, 95% CI 0.694–1.451, respectively). When we analyzed OS according to tumor stage (locally advanced and metastatic), group A and B showed comparable median OS (15.8 vs 13.5 months in locally advanced PDA; 8.6 vs 9.8 months in metastatic PDA, respectively) There were no significant differences in terms of hematologic toxicities except Gr 3 or 4 thrombocytopenia (Group A 3.4%; B 13.2%, P = 0.028). Fatigue and diarrhea were observed more often in Group B than in group A (47.4% vs 10.2%, P = 0.000; 18.4% vs 4.5%, P = 0.010, respectively), all of which were manageable. More patients in group B received dose adjusted FOLFIRINOX than in group A, although there was no statitical significance. Conclusions: FOLFIRINOX could be considered as the first-line chemotherapy for elderly patients with advanced PDA as well as non-elderly patients when dosage modified appropriately, given comparable efficacies and acceptable and manageable toxicities. More studies are warranted to confirm this issue.

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Carboplatin-Paclitaxel Versus Cisplatin-Ifosfamide in the Treatment of Uterine Carcinosarcoma: A Retrospective Cohort Study

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000215 ◽

2014 ◽

Vol 24 (7) ◽

pp. 1256-1261 ◽

Cited By ~ 6

Author(s):

Domenica Lorusso ◽

Fabio Martinelli ◽

Maria Mancini ◽

Italo Sarno ◽

Antonino Ditto ◽

...

Keyword(s):

Overall Survival ◽

Area Under The Curve ◽

Progression Free Survival ◽

Oncologic Outcomes ◽

Uterine Carcinosarcoma ◽

Suitable Alternative ◽

Free Survival ◽

Gynecology And Obstetrics ◽

Group A ◽

Group B

ObjectiveUterine carcinosarcoma (CS) is a rare neoplasm whose adjuvant treatment has not been yet defined. We report on the activity and toxicity of cisplatin-ifosfamide and carboplatin-paclitaxel as adjuvant treatments for patients with uterine CS.MethodsData of International Federation of Gynecology and Obstetrics (FIGO) stage I to IV uterine CS patients treated between 2006 and 2012 with adjuvant chemotherapy (cisplatin 20 mg/mq and ifosfamide 1500 mg/mq day 1 to 4 every 3 weeks plus prophylactic Granulocyte colony-stimulating factor (G-CSF) support [group A] or carboplatin area under the curve -5 (AUC-5) and paclitaxel 175 mg/mq d1q21 [group B]) were retrospectively reviewed. Progression-free survival, overall survival, and chemotherapy-related toxicities were compared between the 2 groups. A subanalysis of oncologic outcomes according to the sarcomatous component (homologous vs heterologous) was performed.ResultsForty-six women were evaluated—21 in group A and 25 in group B. At a median follow-up of 30 months, the median progression-free survival was 11.6 months (95% confidence interval [CI], 6.3–16.9) and 16.6 months (95% CI, 14.7–18.5) for group A and B, respectively (P= 0.20). The median overall survival was 17.1 months (95% CI, 12.6–21.5) and 35.1 months (95% CI, 26.3–43.7) for group A and B, respectively (P= 0.14). No differences were identified among heterologous or homologous components according to chemotherapy treatment. Toxicity profiles widely differ between treatment arms.ConclusionsBecause of the super imposable activity and the better toxicity profile, carboplatin-paclitaxel may be a suitable alternative to cisplatin-ifosfamide in the treatment of uterine CS.

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Randomized Phase II Study of Temozolomide and Radiotherapy Compared With Radiotherapy Alone in Newly Diagnosed Glioblastoma Multiforme

Journal of Clinical Oncology ◽

10.1200/jco.2005.00.331 ◽

2005 ◽

Vol 23 (10) ◽

pp. 2372-2377 ◽

Cited By ~ 167

Author(s):

Helen Athanassiou ◽

Maria Synodinou ◽

Evagelos Maragoudakis ◽

Mihalis Paraskevaidis ◽

Cosmas Verigos ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Malignant Gliomas ◽

Progression Free Survival ◽

Combined Modality Treatment ◽

Newly Diagnosed ◽

Randomized Phase Ii ◽

Group A ◽

One Year ◽

Group B

Purpose Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM. Patients and Methods One hundred thirty patients with pathologically confirmed, newly diagnosed GBM were randomly assigned (110 assessable patients) to receive either TMZ 75 mg/m2/d orally, concomitantly with RT (60 Gy in 30 fractions; group A, n = 57), followed by six cycles of TMZ (150 mg/m2 on days 1 through 5 and 15 to 19 every 28 days), or RT alone (60 Gy in 30 fractions; group B, n = 53). Results Median time to progression was 10.8 months in group A and 5.2 months in group B (P = .0001). One-year progression-free survival rate was 36.6% in group A and 7.7% in group B. Median overall survival (OS) time was also significantly better in group A versus group B (13.4 v 7.7 months, respectively; P < .0001), as was the 1-year OS at 56.3% v 15.7% (P < .0001), respectively. Toxicity was mainly hematologic. One patient with grade 4 myelotoxicity died as a result of sepsis. The other side effects were mild. Conclusion TMZ combined with RT (concomitantly and sequentially) seems to be more effective than RT alone in patients with newly diagnosed GBM. The combined-modality treatment was well tolerated.

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Results of Salvage Autologous Stem Cell Transplantation (ASCT) for Relapsed Multiple Myeloma (MM) in the Era of Novel Agents: Outcome of Patients (Pts) Receiving Prior Bortezomib (BTZ)-Based Therapy

Blood ◽

10.1182/blood.v128.22.5821.5821 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5821-5821 ◽

Cited By ~ 2

Author(s):

Sara Farshchi Zarabi ◽

Esther Masih-Khan ◽

Christine Chen ◽

Vishal Kukreti ◽

Anca Prica ◽

...

Keyword(s):

Maintenance Therapy ◽

Induction Therapy ◽

Research Funding ◽

Chemotherapeutic Agents ◽

Novel Agents ◽

Remission Induction ◽

Group A ◽

Group B ◽

Relapsed Disease ◽

The Impact

Abstract Background: A second (salvage) ASCT has frequently been offered to MM patients with relapsed disease who experience benefit from the first procedure. We have previously reported that pts undergoing a salvage ASCT in the era of VAD or thalidomide (thal) have a median progression-free survival (PFS) of 19 months (mos). The best results were observed in pts who experienced ≥ 2 year benefit after their first ASCT (Jimenez-Zepeda VH et al. Biol Blood Marrow Transplant 2012; 18: 773-9). However, the utility of this approach after the introduction of novel chemotherapeutic agents--such as bortezomib (BTZ)--remains unclear. Initially, provincial funding for BTZ in Ontario was provided only for relapsed disease. However, in 2007, the combination of either BTZ + dexamethasone (BTZ-dex) or cyclophosphamide, BTZ + dex (CyBorD) was adopted as the standard induction regimen for newly diagnosed pts before ASCT performed as part of first-line therapy. We now examine the results of salvage ASCT in our centre after the availability of BTZ. Methods: We used the Princess Margaret Myeloma Database to identify and characterize patients with relapsed MM who had received a bortezomib (BTZ)-based regimen for remission induction prior to their first ASCT or for re-induction before salvage ASCT. A retrospective chart review was performed to investigate the PFS and overall survival (OS) outcomes of these pts. Results: Between 01/2005 and 07/2015, 64 pts with MM who had previously received BTZ-based therapies underwent salvage ASCT for relapsed disease at our centre (Table 1). Median age was 56.9 yrs (range 37-67.3); 37 (58%) were male. ISS stage was 1 in 32 (50%), 2 in 16 (25%), 3 in 14 (22%) and NA in 2 (3%). The median interval between first and salvage ASCT for all pts was 48.6 mos (range 26.9-130.3), reflecting our policy of preferentially offering salvage ASCT to pts with at least a 2-yr benefit from the first transplant; the median time between re- induction therapy and salvage ASCT was 6.3 mos (range 0.3-95.9). Group A pts (n=27) had received BTZ-based therapy before their first ASCT; 48% of these also received BTZ-based regimens again prior to salvage ASCT. Pts in Group B (n=37) received BTZ-based regimens before the salvage transplant only, while induction therapy before the first ASCT consisted of VAD (21), dex alone (8), thal + dex or other regimens (5). Twenty-two (34%) of the pts received maintenance therapy between the first and salvage ASCT (most often thal-based), while 35 (55%) of the pts received maintenance therapy following salvage ASCT (most frequently lenalidomide [len]-based). The survival outcomes are summarized in Table 2. Median duration of follow-up (F/U) following salvage ASCT was 19.1 mos (range 0.8-96.4). One patient (1.6%) died several days following salvage ASCT. No other transplant-related mortality occurred. The median PFS following salvage ASCT was 19.1 mos (range 0.8- 87.5) with a median OS of 26.5 mos (range 0.8-101.9) in all pts. The median PFS after salvage ASCT was 15.8 mos for Group A and 25.2 mos for Group B pts. Conclusions: Even in the era of novel agents, salvage ASCT may provide PFS benefit to pts with relapsed MM who were previously treated with a BTZ-based regimen. However, the details of the optimal approach in this setting are not certain, including the impact of maintenance therapy given after the first and/or salvage ASCT. We are performing additional analyses of this population to try to identify factors associated with the best outcomes. Disclosures Kukreti: Celgene: Honoraria; Lundbeck: Honoraria; Amgen: Honoraria. Prica:Janssen: Honoraria. Tiedemann:Novartis: Honoraria; Celgene: Honoraria; Takeda Oncology: Honoraria; BMS Canada: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Trudel:Celgene: Honoraria; Novartis: Honoraria; Glaxo Smith Kline: Honoraria, Research Funding; Oncoethix: Research Funding. Reece:Merck: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.

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