Sequential High-Dose Dexamethasone and Response Adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Chemotherapy Followed by High-Dose Therapy with ASCT for Newly Diagnosed Multiple Myeloma; Open-Labeled, Multicenter Phase 2 Study (KMM-94 Study)-Interim Analysis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3106-3106
Author(s):  
Jae Hoon Lee ◽  
Junshik Hong ◽  
Jin Seok Kim ◽  
June-Won Cheong ◽  
Cheolwon Suh ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Conflicts Of Interest ◽  
Poor Response ◽  
New Drugs ◽  
Induction Treatment ◽  
High Dose ◽  
Fish Analysis ◽  
Newly Diagnosed ◽  
Younger Patients ◽  
High Dose Dexamethasone

Abstract Abstract 3106 Background: Induction therapy followed by ASCT is the standard therapy for the newly diagnosed younger patients with MM. Recently, new drugs such as lenalidomide or bortezomib have shown the promising results as an induction treatment. However, these drugs are not available in many countries as a front line treatment and many different type of induction treatment regimens including old regimens are used. We evaluate the efficacy and safety of the brief course of high dose dexamethasone (HD) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: One hundred fifty five newly diagnosed patients with MM from 23 institutions received 2 cycles of HD followed by PAD or VAD chemotherapy according to the response to the HD. PAD 4 cycles were given to nonresponsders and VAD 2 cycles were given to who achieved more than PR to HD. The primary endpoint was CR + nCR rate after ASCT. Among 155 patents enrolled this study from November 2009, 29 patients (19%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred fifty five patients (88 male, 69 female) were enrolled (median age; 57). 34 (22%) patients had ISS stage I, 64 (41%) stage II and 55 (35%) stage III. Thirty six (26%) patients had abnormal cytogenetics. In FISH analysis, there were 25% del13, 9% del17, 21% t (4; 14), 13% t (14; 16) and 26% t (11; 14). Among the 115 evaluable patients, CR + PR rate was 53% (61/115) after 2 cycles of HD. 61 patients (53%) received subsequent VAD chemotherapy and 54 patients (47%) received PAD chemotherapy. Among the evaluable patients, CR + PR rate after induction therapy was 83% (79%, 48/61 in VAD group vs. 89%, 48/54 in PAD group). 95 patients finished ASCT. CR + nCR rate after ASCT were 74% (74% in VAD group vs 73% in PAD group). Mortality rate of this trial was 15% (17/115). The cause of death was disease progression (n=5), bleeding (n=1) and infections (n=11). Among 115 patients in whom VAD or PAD chemotherapy was actually performed, 1 year OS was 88.1%. (VAD arm 90.7% versus PAD arm 86.1% (P=0.105): median follow-up; 16.6 months). Conclusion: Risk adapted approach using initial HD response showed good response results after ASCT compared with previous trial (CR + nCR rate of IFM 2005-01 trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who showed poor response to HD also showed similar good response rate after ASCT compared with the patients who had good response to HD in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Our data shows that almost half of the patients who responded to HD can be saved of novel agents during induction treatment, and PAD can successfully rescue the other half who are not sensitive to HD. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.

Sequential High-Dose Dexamethasone and Response Adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Induction Chemotherapy Followed by High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma; Open-Labelled, Multicenter Phase 2 Study (KMM-94 Study)-Interim Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2044-2044
Author(s):  
Jin Seok Kim ◽  
Cheolwon Suh ◽  
June-Won Cheong ◽  
Kihyun Kim ◽  
Yang Soo Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Chemotherapy ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Younger Patients ◽  
High Dose Dexamethasone

Abstract Abstract 2044 Background: Induction treatment followed by autologous stem cell transplantation (ASCT) is the standard therapy for the newly diagnosed younger patients with multiple myeloma (MM). Although new drugs such as lenalidomide or bortezomib have been shown the promising results as induction treatment, many different type of induction treatment regimens still have been used. We evaluate the efficacy and safety of the short course of high dose dexamethasone (HD dexa) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: 107 newly diagnosed patients with MM from 21 institutions received 2nd cycles of HD dexa followed by PAD or VAD chemotherapy according to the response to the initial high dose dexamethasone. The primary endpoint was complete response (CR) + near CR rate after ASCT. Among 107 patents enrolled this study from November 2009, 25 patients (23%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred seven patients (58 male, 49 female) were enrolled (median age; 56). 26 (24%) light chain disease were included. 31 (29%) patients were D-S stage II and 67 (63%) were stage III. According to the ISS, 23 (22%) patients had stage I, 51 (48%) had stage II and 33 (31%) had stage III. 26 (24%) patients had abnormal cytogenetics. There were 31% del13, 7% del17, 19% t(4;14), 15% t(14;16) and 28% t(11;14) in FISH analysis. Among the 82 evaluable patients, CR + PR rate was 48% (39/82) after 2nd cycles of HD dexa therapy. 39 patients (48%) received subsequent VAD chemotherapy and 43 patients (52%) received PAD chemotherapy. Among the 64 patients finished VAD or PAD chemotherapy, CR + PR rate was 83% (79%, 26/33 in VAD group vs. 87%, 27/31 in PAD group). 56 patients were finished ASCT until now. CR + near CR rate after ASCT were 61% (58% in VAD group vs 63% in PAD group). Mortality rate of this trial was 13% (11/82). The cause of death was disease progression (n=3), bleeding (n=1) and infections (n=7). Among 82 patients in whom VAD or PAD chemotherapy was actually performed, 1 year overall survival (OS) rate was 84.7%. 1 year survival rate was 93.8% versus 77.2% (P=0.049) with VAD versus PAD (median follow-up; 9.1 months). Conclusion: Risk adapted approach using initial steroid response showed good response results after ASCT compared with previous trial (CR + near CR rate of IFM 2005-01trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who had poor response to HD dexa also showed similar good response rate after ASCT compared with the patients who had good response to HD dexa treatment in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.

The Use of Purine Analogues Does Not Aggravate Infectious Complications During Induction and Consolidation Therapy of Acute Myeloid Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1011-1011
Author(s):  
Marek Seweryn ◽  
Jerzy Wojnar ◽  
Dariusz Kata ◽  
Slawomira Kyrcz-Krzemien
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Infectious Complications ◽  
Induction Treatment ◽  
High Dose ◽  
Consolidation Therapy ◽  
Purine Analogues ◽  
Acute Myeloid

Abstract Abstract 1011 Poster Board I-33 Background: Addition of purine analogues to standard induction therapy of acute myeloid leukemia (AML) had previously been demonstrated to increase complete remission rate. The aim of this study was to analyze whether the use of cladribine or fludarabine during induction and consolidation increases the risk of infectious complications. Material and methods: 118 AML patients, included in two consecutive randomized trials between 1999-2006 in a single centre were analyzed. Induction therapy consisted of daunorubicin + cytarabine (DA-7, n=53) alone or in combination with cladribine or fludarabine (DAC-7 + DAF-7, n=65 ). Consolidation included one course of high-dose AraC + mitoxantrone and one course of high-dose AraC +/- purine analogues. A median age was 45(17-58) years and 48(20-60) years for patients treated with and without purine analogues, respectively. Results: The frequency of neutropenic fever as well as microbiologically documented bacterial, fungal and viral infections during induction and consolidation did not differ between two compared groups - receiving or not purine analogues. Time to infection occurrence and infection duration were similar in both study groups. During induction and both consolidation treatments significant lower values of lymphocytosis were observed in the group of patients treated with purine analogues. There was a slight tendency to increased rate of mucositis for patients treated with purine analogues (60% vs. 44.3%, p=0.07) during induction treatment, while infections affecting skin and soft tissues were significant frequent for patients treated without purine analogues (43.3% vs. 18%, p=0.03) during second consolidation treatment (high dose AraC). The usage of intravenous anti-infectious medications (antibiotics, antifungal, antiviral) and periods of hospitalization did not differ between two groups in this study. Conclusions: We conclude that the use of purine analogues, either cladribine or fludarabine along with conventional induction and consolidation therapy does not aggreviate infectious complications in adults with AML. Disclosures: No relevant conflicts of interest to declare.

Adding The KIT Inhibitor Dasatinib (DAS) To Standard Induction and Consolidation Therapy For Newly Diagnosed Patients (pts) With Core Binding Factor (CBF) Acute Myeloid Leukemia (AML): Initial Results Of The CALGB 10801 (Alliance) Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 357-357 ◽  
Author(s):  
Guido Marcucci ◽  
Susan Geyer ◽  
John Zhao ◽  
Andrew J Caroll ◽  
Donna Bucci ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Rapid Screening ◽  
Induction Treatment ◽  
High Dose ◽  
Protein Chain ◽  
Consolidation Therapy ◽  
Newly Diagnosed ◽  
Early Results

Abstract Among the prognostic cytogenetic and molecular aberrations in AML, t(8;21)(q22;q22) and inv(16)(p13q22) and their corresponding molecular rearrangements RUNX1/RUNX1T1 and CBFB/MYH11 (each involving a gene encoding a protein chain of the key transctiption factor CBF), predict for a favorable outcome in pts receiving consolidation with high-dose cytarabine (HiDAC) after achievement of complete remission (CR). However, approximately 40% of these pts eventually relapse. Approximately 25% of CBF AML pts carry gain-of function mutations in the KIT gene. These mutations result in a constitutively active tyrosine kinase (TK) that contributes to aggressive leukemia growth, and is associated with unfavorable outcome. In addition, CBF AML pts with wild type KIT overexpress this protein, and this is also associated with an inferior outcome. Therefore, inhibiting KIT with DAS is a rational therapeutic strategy in CBF AML. We report here on a phase II trial that combined DAS with standard chemotherapy for CBF AML. Enrollment required molecular confirmation of CBF AML by the Alliance Molecular Pathology central lab using RT-PCR and Sanger sequencing-based assays. Overall, 779 patients were screened for CBF; 69 were found to be CBF-positive and 61 were subsequently enrolled. Newly diagnosed RUNX1/RUNX1T1 or CBFB/MYH11-positive pts received induction chemotherapy with cytarabine (C) 200 mg/m2/day continuous intravenous (IV) infusion on days 1-7, daunorubicin (DNR) 60 mg/m2/d IV bolus on days 1-3 and DAS 100 mg/d PO on days 8-21. Pts with residual disease (>5% blasts) on day 21 after first induction received a re-induction treatment with same doses of C on days 1-5, DNR on days 1-3 and DAS on days 6-19. Pts who achieved CR received consolidation therapy with HiDAC 3000 mg/m2 over 3 hours (if <60 yrs old) or 1000 m/m2 (if older) q12h on days 1,3,5 and DAS 100 mg/d PO on days 6-26 x 4 courses. Pts who remained in CR after consolidation treatments received continuation treatment with DAS 100mg/d PO x 12 months. The primary goal of this study was to insure that the CR rate and survival during induction were not inferior to historical outcomes. Between April 2011 and January 2013, we completed the planned accrual of 61 adult CBF AML pts. Median age was 51 years (yrs; range: 19.6 to 85 yrs), and 15 pts (24%) were older (>60 yrs). Half of pts were male (51%) and a majority were Caucasian (75%). Of all 61 pts, 65% were CBFB/MYH11-positive and 35% were RUNX1/RUNX1T1-positive. Treatment was started on average 4 days from molecular diagnosis (range: 0 to 11 days). To date, 51% of pts are still undergoing treatment; 4 pts died on treatment (2 older), 7 (4 older) had an adverse event requiring treatment interruption, and 6 refused to complete the treatment (mainly the continuation component). Observed toxicities were those expected with C and DNR (hematologic and non-hematologic) and with DAS (nausea, liver toxicity). 55 pts are currently evaluable for treatment-related toxicity. The most common grade 4 toxicities were sepsis (5), acute kidney injury (3), and respiratory failure (3). Grade 5 toxicities included respiratory failure (1) and sepsis (2). Two of these pts died during induction (respiratory failure, sepsis); both were older and CBFB/MYH11. One pt died from sepsis during consolidation in CR (CBFB/MYH11, 48 yrs). The 30-day survival rate was 97% (95% CI: 89% to 99.6%) overall (98% in younger and 93% in older pts). Of 59 pts currently evaluable for response, 54 (92% of all pts; 96% younger and 80% older) achieved CR. Of the 5 patients who failed to achieve CR, 2 had RUNX1/RUNX1T1 and 3 had CBFB/MYH11. Among the 54 CR pts, no younger pt has relapsed, while 2 older pts with CBFB/MYH11 have relapsed. The median follow-up (f/u) was 11.2 months (range: 1.2 to 23.2 mos.). The 1-yr DFS and OS rates were respectively 90% and 87% for all pts; 97% and 95% for younger pts, and 63% and 62% for older pts, respectively. Early results from this study show that 1) rapid screening for CBF AML is feasible within a cooperative group, 2) DAS plus chemotherapy in CBF AML pts is tolerable including in older pts, and 3) the initial clinical outcomes are at least comparable to those historically observed in this patient population. Patients continue to be followed for survival endpoints. Molecular characterization for KIT mutations and expression levels of marrow and blood blasts is ongoing and will be correlated with toxicity and clinical outcome. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Benefit of Two Additional Cycles of Bortezomib/Thalidomide/Dexamethasone (VTD) Induction Therapy Compared to Four Cycles of VTD for Newly Diagnosed Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3252-3252
Author(s):  
Yoojin Lee ◽  
Kihyun Kim ◽  
Sang Kyun Sohn ◽  
Dongwon Back ◽  
Joon Ho Moon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Prognostic Factor ◽  
Induction Therapy ◽  
Conflicts Of Interest ◽  
Stage I ◽  
High Dose ◽  
Newly Diagnosed ◽  
Favorable Prognostic Factor

Abstract Introduction Four cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapy for patients aged less than 65 years with newly diagnosed multiple myeloma (NDMM). Complete remission (CR) status before ASCT is an important prognostic factor for progression-free survival (PFS). We analyzed whether two additional cycles of VTD improved the pre- and post-transplant responses as well as PFS compared to the four cycles of VTD induction therapy. Methods A total of 222 patients with NDMM between September 2014 and August 2016 from eleven hospitals in South Korea were included in the current study. The patients received at least four or more cycles of VTD induction therapy before administration of high-dose therapy (HDT, melphalan 200mg/m2) followed by ASCT. VTD regimen was consisted of bortezomib subcutaneous infusion (1.3 mg/m2 on days 1, 4, 8, and 11), thalidomide (100 mg daily), and dexamethasone (40 mg on days 1-4, 8-11), which was administered every 4 weeks. Results The median age was 57 years (range 30−64 years), and 120 patients (61.9%) were male. Revised international scoring system (R-ISS) classified 59 (30.4%), 86 (44.3%), and 49 patients (25.3%) as stage I, II, and III, respectively. VTD induction was administered 4 cycles in 194 patients (VTD4, 67.5%) and more than 4 cycles in 63 (VTD6, 32.5%) before HDT. Patient characteristics at diagnosis did not differ between VTD4 and VTD6. CR rate before HDT was significantly higher in VTD6 than VTD4 (31.7% vs 13.0%, P = 0.003). However, CR rate after HDT/ASCT was similar between VTD4 and VTD6 (69.0% vs 65.5%, P = 0.726). There was no difference in the incidence of peripheral neuropathy (PN) (≥ grade 2 or that required dose reduction) between two groups. The median follow-up duration was 18.0 months (range 7.0-43.8 months). The 2-year PFS did not differ between the two groups (51.7 ±5.7% in VTD4 and 62.1±8.6% in VTD6, P = 0.240). Multivariate analysis revealed that the achievement of CR was a favorable prognostic factor for PFS (HR 0.27 [0.08−0.90], P = 0.034). Deletion 17p (HR 2.87 [1.01−7.92], P = 0.048) and t(4;14) (HR 3.38 [1.76−6.48], P < 0.001) in FISH were adverse prognostic factors for PFS. Patients with stage I/II by R-ISS receiving additional two cycles of VTD showed prolonged PFS (median PFS not reached vs. 27.6 months, P = 0.034). In the multivariate analysis, VTD6 was a favorable prognostic factor for PFS for patients with stage I/II by R-ISS, (HR 0.11 [0.02−0.52], P = 0.005). Conclusion CR rates increased with additional cycles of VTD induction therapy for NDMM. However, the PFS benefit was observed only in patients with R-ISS stage I/II. For patients with high-risk MM, intensive induction therapy that overcome poor prognostic factors should be administered to improve long-term outcomes. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Rates of CR with and without Measurable Residual Disease after Induction Treatment with "7+3" or Azacitidine/Decitabine for Newly-Diagnosed AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2792-2792
Author(s):  
Todd Yezefski ◽  
Roland B. Walter ◽  
Pamela S. Becker ◽  
Paul C. Hendrie ◽  
Vivian Oehler ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Survival Rates ◽  
Gemtuzumab Ozogamicin ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Newly Diagnosed ◽  
Multiparametric Flow Cytometry ◽  
Measurable Residual Disease

Abstract Introduction The importance of measurable residual disease (MRD) at time of complete remission (CR) as a predictor of relapse and/or survival either after allogeneic transplant (HCT) or chemotherapy without HCT is widely recognized (Chen et al. JCO 2015;33:1258-64). Hence, a goal of induction therapy might be not only to produce CR, but CR without MRD. Here we compare rates of CR with and without MRD after induction therapy with either (1) "7+3", (2) azacitidine (aza) or decitabine (dec) alone (aza/dec alone), or (3) regimens containing aza or dec with other low intensity treatment (aza/dec combos). Given reportedly similar survival rates with 7+3 and aza/dec alone, and the contribution of CR without MRD to survival, we hypothesized that while CR rates are higher with 7+3, there would be relatively less difference in rates of CR without MRD. Methods We analyzed 272 patients with newly diagnosed, high-risk MDS (10-20% blasts) or AML (> 20% blasts) treated with the following regimens: 7+3 (139 patients), aza/dec alone (64) or aza/dec combos (69), the latter most commonly involving gemtuzumab ozogamicin +/- vorinostat. Cytogenetic risk and response to treatment were assessed per ELN guidelines, and MRD was assessed via 10- color multiparametric flow cytometry as previously described (Chen et al. JCO 2015;33:1258-64). Results As expected, patients given 7+3 were younger, with median ages of 53 for 7+3, 63 for aza/dec alone, and 58 for aza/dec combos. In 7+3, cytogenetic risk was favorable in 29%, intermediate in 26%, and poor in 45%; for aza/dec alone 5% were favorable, 44% intermediate, and 51% poor; and for aza/dec combos, 12% were favorable, 30% intermediate, and 58% poor. As expected, CR rates were higher with 7+3: 72% vs. 14% for aza/dec alone and 17% for aza/dec combos. Rates of CR w/o MRD were also higher with 7+3: 58% vs. 9% for aza/dec alone and 13% for aza/dec combos (p<0.001), while rates of CR with MRD were more similar (14% 7+3 vs. 5% aza/dec alone and 4% for aza/dec combos. Rates of CR w/o MRD were higher with favorable risk cytogenetics (78%) than intermediate risk (24%) or poor risk (22%). The same was true considering only either the aza/dec alone group (67% vs 4% vs 9%) or the aza/dec combo group (50% vs 5% vs 10%.) Conclusion The higher CR rate seen with 7+3 than with aza/dec or its combinations is paralleled by a higher rate of CR without MRD. Multivariate analyses are currently analyzing the relation between relapse/survival and CR without MRD, cytogenetic risk, and treatment, and whether the effect of CR without MRD on these outcomes is the same with 7+3 and aza/dec or its combinations. Assuming, as expected, RFS and survival in the current population is approximately similar regardless of treatment with 7+3, aza/dec or its combinations, the failure of 7+3 to produce better survival despite higher rates of CR without MRD would suggest limitations in the use of CR without MRD as a surrogate for RFS and survival. The similar effect of cytogenetics on CR without MRD rates with 7+3, aza/dec alone or aza/dec combos suggests a qualitative similarity between these regimens that is perhaps more than often appreciated. Disclosures No relevant conflicts of interest to declare.

Favorable Responses to Novel Agents for Multiple Myeloma in African American Patients,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4213-4213
Author(s):  
Santosh Saraf ◽  
Pritesh R. Patel ◽  
Howard Ozer ◽  
David Peace ◽  
Sangeetha Nimmagadda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African Americans ◽  
Induction Therapy ◽  
Partial Remission ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
High Dose Chemotherapy ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant

Abstract Abstract 4213 Multiple myeloma (MM) accounts for 10% of hematologic malignancies in the U.S. African Americans (AA) have twice the risk of developing multiple myeloma and, in previous studies, a higher mortality rate when compared to non-African Americans (non-AA). In recent years, clinical outcomes for patients with MM have improved as a result of new agents, such as immunomodulatory drugs (IMiDs) and bortezomib. However, the therapeutic impact of these new therapies in AA vs. non-AA patients has not been evaluated. In this study, 53 consecutive patients (23 AA, 30 non-AA) with newly diagnosed MM were retrospectively analyzed after induction treatment with thalidomide/dexamethasone (n=22), lenalidomide/dexamethasone (n=8), bortezomib/dexamethasone (n=5), bortezomib/thalidomide/dexamethasone (n=3), lenalidomide/bortezomib/dexamethasone (n=12), or an IMiD plus melphalan (n=3). AA and non-AA patients were comparable for age, immunoglobulin isotype, MM stage of disease, serum β2microglobulin and albumin levels, and cytogenetic abnormalities including del13 (27% vs. 38%, respectively, p=NS). When measured according to international uniform criteria, the response rate to induction therapy was not statistically different between AA and non-AA patients: complete remission (CR, 22% vs. 21.4%), very good partial remission (VGPR, 26% vs. 21.4%), or partial remission (PR, 43.4% vs. 32.1%). However, the rate of stable/progressive disease following induction therapy was significantly higher in non-AA patients (p = 0.03). Of 53 patients, 34 received high-dose chemotherapy followed by autologous stem cell transplant (ASCT). In this group, the CR + VGPR rate following ASCT was significantly higher in AA compared with non-AA patients (59% vs. 35%, p=0.0007). At a median follow up of 47 months, the relapse rate was 59% in AA and 46% in non-AA patients (p=NS) and the median time to progression (TTP) was 9.1 months in both groups. Five patients (9%) died. All deaths occurred in the non-AA cohort and in 4/5 cases death was due to disease progression. In conclusion, our findings demonstrate that despite their increased disease risk, AA patients with MM have a favorable outcome that is equivalent to that of non-AA patients when treated with IMiDs and/or bortezomib. Disclosures: No relevant conflicts of interest to declare.

Assessment Of The Value Of a Day 14 Bone Marrow In Newly Diagnosed AML

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5002-5002
Author(s):  
Todd Allen Yezefski ◽  
Hu Xie ◽  
Pamela S. Becker ◽  
John M. Pagel ◽  
Roland B. Walter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Induction Therapy ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Similar Proportion ◽  
High Dose ◽  
Newly Diagnosed ◽  
Resistant Disease ◽  
High Dose Cytarabine

Abstract Introduction Mangement of AML typically calls for a bone marrow aspirate 7-10 days after completion of induction therapy with standard or high-dose cytarabine (HiDAC)-containing regimens (day 14 marrow). If this marrow contains >5-10% blasts, National Comprehensive Cancer Network guidelines recommend a second course of induction therapy. However, nearly 70% of patients who have persistent blasts in a day 14 marrow do not begin reinduction within 1 week. Additionally, at least in patients given higher doses of cytarabine as part of induction therapy, blast counts often continue to decrease between days 14 and 21, and many such patients will achieve complete remission (CR) without a second induction. These findings call into question the value of a day 14 marrow. Methods Our database contained 154 patients with newly diagnosed AML or MDS with 10-19% blasts seen in our hospital from 2008-2013. Patients lived at least 21 days after receiving induction therapy with regimens containing standard-dose cytarabine (114 patients, typically given “3+7” ) or high-dose cytarabine (40 patients). The treatments were not given on protocol, thus granting physicians discretion to determine when to examine the marrow. Marrow exams performed between days 10 and 17 after starting induction were considered a “day 14 marrow.” Response was assessed at least 21 days from the start of the initial induction course. Our goals were (1) to identify pretreatment factors (described below) associated with the decision to obtain a day 14 marrow and (2) to determine the influence obtaining a day 14 marrow had on the likelihood of CR on course 1, after accounting, by multivariable logistic regression, for age, cytogenetic risk (SWOG criteria), pretreatment blast % (morphologic count in marrow; peripheral blood if no marrow available), and type of AML (de novo vs. secondary). Results 116 of 154 patients (75%) had a day 14 marrow. Patients who had and did not have a day 14 marrow were similarly-aged (average 53 in both groups), had similar pretreatment blast percentages (52% vs 47%, respectively), and had a similar proportion with de novo AML (66% vs 68%). Patients who had a day 14 marrow more often received 3+7 (79% of standard-dose cytarabine patients had a day 14 marrow vs 65% of HiDAC, p=0.06). Only 60% of patients with favorable risk cytogenetics had a day 14 marrow vs 79% of patients with intermediate or unfavorable risk (p=0.03). Considering the 3+7 group separately, only a higher pretreatment blast count predicted the likelihood of a day 14 marrow (53% with a day 14 marrow vs 38% without, p=0.02). No factors were predictive in the HiDAC group. As expected, favorable cytogenetics were associated with a higher CR rate while age, pretreatment blast %, and de novo vs secondary AML did not influence CR. After accounting for these covariates, there was no difference in the rate of CR between patients who did and did not have a day 14 marrow (66% vs 74%, p=0.61). The same was true when standard and high-dose cytarabine were analyzed separately (p=0.80 and 0.26, respectively). 18 patients with a day 14 marrow had resistant disease and received a second induction course; of these, two achieved CR. Likewise, two patients without a day 14 marrow were reinduced for resistant disease, and one entered CR. While the response to the second induction was not included in the analysis, results would not be expected to vary significantly given the CR rates with the second course. Conclusions These results suggest that while patients are more likely to have a day 14 marrow if they have intermediate- or poor-risk cytogenetics and receive 3+7, the decision to obtain a day 14 marrow does not lead to a higher CR rate. Disclosures: No relevant conflicts of interest to declare.

CKS1B Over-Expression Significantly Predicts for a Lower Rate of Response to Primary Therapy with Thalidomide-Dexamethasone (Thali-Dex) for Newly Diagnosed Multiple Myeloma (MM) Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 371-371
Author(s):  
Matteo Renzulli ◽  
C. Terragna ◽  
N. Testoni ◽  
E. Montanari ◽  
P. Tosi ◽  
...  
Keyword(s):  
Response To Therapy ◽  
Remission Induction ◽  
Lower Probability ◽  
High Dose ◽  
Fish Analysis ◽  
Primary Therapy ◽  
Newly Diagnosed ◽  
Rt Pcr ◽  
Over Expression ◽  
The Relationship

Abstract In MM tandem duplication and jumping translocations of the q21 band of chromosome (chr.) 1 are acquired during progression of the disease and can lead to chr.1q amplification. In several studies, chr. 1 amplification has been linked to poor prognosis after both conventional and high-dose chemotherapy. Recently, a subset of genes mapping on 1q21 band has been identified, whose increased expression may be due to increased DNA copy number. Among these genes, CKS1B has been one of the most significantly upregulated. CKS1B regulates SCF skp2 mediated ubiquitination and proteolysis of the cyclin dependent kinase inhibitor p27Kip1, whose low expression has been reported to be an independent adverse prognostic factor in MM patients. Aim of the present study was to investigate the relationship between CKS1B expression and response to primary therapy with thali-dex in a large series of patients with newly diagnosed MM. Secondary endpoint was to explore the relationship between CKS1B expression and del(13), as assessed by FISH analysis, and t(4;14), as evaluated by an RT-PCR assay designed to detect the presence of IgH/MMSET fusion gene. A total of 132 patients were analyzed. The presence of t(4;14) and CKS1B expression were investigated in all patients, while del(13) was studied in 129/132 patients. CKS1B expression was evaluated by Real-time RT-PCR. CKS1B values were separated in four different quartiles, with expression levels increasing progressively from quartile 1 to 4. Response to therapy was evaluated according to the criteria proposed by Bladè et al. The Fisher test and the Mann-Whitney test were applied for statistical analysis. On an intent-to-treat basis, the overall probability to respond (≥ partial response, PR) to up-front thali-dex therapy was 71%, while 38 patients (29%) either did not respond (NR) or progressed. Median CKS1B expression value was significantly higher in NR in comparison with patients who attained at least a PR: 1.42 (range 0.15–52.35) vs. 0.89 (range 0–11.88), respectively (p=0.01). In particular, the proportion of NR patients in the CKS1B expression quartile 4 was significantly higher as opposed to the frequency of NR in the CKS1B expression quartiles 1 to 3 (45.5% vs. 23.2%, respectively; p= 0.02). CKS1B over expression did not correlate with the presence of t(4;14) or del(13). Only 6 patients harbouring t(4;14) fell into the CKS1B expression quartile 4, as opposed to 32 patients included into the CKS1B expression quartiles 1–3 (18.2% vs. 32.3%; p, not significant). Similarly, the frequency of del(13) was comparable in the CKS1B expression quartile 4 and in the CKS1B expression quartiles 1–3 (34.4% vs. 44.3%; p, not significant). Likewise, only 2 patients carrying both t(4;14) and del(13) fell into the CKS1B expression quartile 4, as opposed to 15 patients who fell into the CKS1B expression quartiles 1–3 (6.5% vs. 15.3%; p, not significant). In conclusion, in patients with newly diagnosed MM, CKS1B over expression at baseline predicts for a significantly lower probability of response to primary remission induction therapy with thali-dex. Poor response to thali-dex conferred by CKS1B over expression is independent from the presence of t(4;14) and/or del(13). Supported by Università di Bologna, Progetti di Ricerca ex-60% (M.C.); Ministero dell’Università e Ricerca Scientifica (MIUR), progetto FIRB, RBAU012E9A_001 (M.C.); and Fondazione Carisbo.

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