Highlights From Key Hematology and Oncology Congresses

Resident Reporter-March 2013
Katie E. Long, PharmD
Lynne Lederman, PhD
PhD, Medical Writer

Prostate Cancer

Dr J. Bellmunt, University Hospital del Mar-IMIM, Barcelona, Spain, presented “Molecular Insights and Treatment Outlook for GU Malignancies.”1 Cabazitaxel, a taxane derivative targeting microtubules, has proven efficacy in castrate-resistant prostate cancer (CRPC) for which docetaxel has failed. Agents with promising results in phase 3 randomized studies in patients with metastatic CRPC include sipuleucel-T, abiraterone acetate, alpharadin, and the antiandrogen MDV3100. Promising agents in phase 2 studies include cabozantinib, custirsen, and dasatinib. Novel immunotherapeutics under investigation include prostate-specific membrane antigen–directed therapy, and the anti-CTLA4 antibody ipilimumab.

Additional presentations and posters on the results of trials in patients with prostate cancer are summarized in Table 1.


Table 1

Breast Cancer

Two studies investigating the optimum duration of trastuzumab therapy were presented at ESMO. X. Pivot, MD, University Hospital J. Minjoz, Besancon, France, presented the PHARE trial results in adjuvant early breast cancer in 3382 patients who were randomly assigned 1:1 to receive 6 or 12 months of trastuzumab therapy. Cardiac toxicity occurred less often in the 6-month group, and 6 months of trastuzumab was noninferior for disease-free survival and overall survival (OS) compared with 12 months of trastuzumab.8 Aron Goldhirsch, MD, Department of Medicine, European Institute of Oncology, Milan, Italy, presented “HERA TRIAL: 2 Years Versus 1 Year of Trastuzumab After Adjuvant Chemotherapy in Women With HER2-Positive Early Breast Cancer at 8 Years of Median Follow-up.” After completion of primary therapy, 5102 women were randomly assigned to trastuzumab every 3 weeks for 1 or 2 years or to observation. Results of this landmark trial showed no difference in OS or time to distant recurrence; however, patients in the 2-year arm experienced a greater decline in left ventricular ejection fraction. The HERA trial confirmed that the benefits of 1 year of trastuzumab remain stable at a median 8 years of follow-up.9

In a satellite symposium moderated by Günther Gastl, MD, Innsbruck Medical University, Innsbruck, Austria, and sponsored by Teva Europe, a panel discussed optimizing the management of chemotherapy in patients with breast cancer. Bryan Hennessy, MD, Beaumont Hospital, Dublin, Ireland, discussed anthra­cycline rechallenge in metastatic breast cancer: pros and cons. Gastl spoke about the 4 phase 3 studies investigating nonpegylated liposomal doxorubicin and its benefits, including decreased cardiac toxicity and a greater maximal dose. Alessandra Gennari, MD, PhD, Galliera Hospital, Genoa, Italy, answered the question, “Is Advanced Breast Cancer the New Chronic Disease of the 21st Century?” Due to the heterogeneous patient population, there is a variety of goals and treatment options for chronic breast cancer. Many of today’s treatments are able to maintain stable disease burden, turning advanced breast cancer into a chronic disease. “Enhancing the Activity of Pegfilgrastim: Lessons From PK and PD” was presented by Armando Genazzani, MD, University of Piemonte Orientale “Amedeo Avogadro,” Novara, Italy. Pharmacokinetic studies of pegylation have shown it increases systemic exposure to drugs secondary to increased distribution and decreased metabolism and excretion. There are a number of granulocyte colony-stimulating factors (G-CSFs) currently in development. Gastl concluded the symposium with a presentation, “New Alternatives for the Prevention of Febrile Neutropenia in Patients With Cancer.” G-CSF is the treatment of choice for prolonged neutropenia, lipegfilgrastim is not inferior to pegfilgrastim, and G-CSFs are cost saving if they prevent hospitalizations due to febrile neutropenia.

Additional presentations of breast cancer trials are summarized in Table 2.

Non–Small Cell Lung Cancer

The phase 3 study of crizotinib versus pemetrexed or docetaxel chemotherapy in patients with advanced ALK-positive non–small cell lung cancer (NSCLC) (PROFILE 1007) was presented by Alice Shaw, MD, Massachusetts General Hospital, Boston, Massachusetts.16 Patients with ALK-positive NSCLC treated with crizotinib, a first-in-class orally available ALK inhibitor, had a significantly higher progression-free survival (PFS) at a median of 7.7 months versus patients treated with chemotherapy (pemetrexed, PFS 4.2 months; docetaxel, PFS 2.6 months or 3.0 months in the chemotherapy group as a whole). The overall response rate (ORR) was 65.3% with crizotinib, significantly higher than that with chemotherapy (19.5%). There was no significant difference between groups in OS because of an 87% crossover rate from chemotherapy to crizotinib. Adverse events (AEs) were tolerable and similar among groups and generally as expected. Quality of life (QOL) improved significantly in those treated with crizotinib versus those treated with
chemotherapy.

Chronic Lymphocytic Leukemia

Dan-Avi Landau, MD, presented “The Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia.”17 His group used whole exome sequencing and single nucleotide polymorphism arrays to analyze subclonal and clonal point mutations and copy number changes in samples from 149 patients with chronic lymphocytic leukemia (CLL). They identified 3 driver mutations – MYD88, trisomy 12, and del(13q) – that were present in nearly all samples and propose that these arise early in CLL development. Other drivers arising at subclonal frequencies are assumed to arise later in CLL development. Of the 18 patients for whom data from 2 distant time points were available, evolution of somatic mutations enriched in putative drivers from subclonal toward clonality was detected in 11; only 1 patient had not received intervening treatment. The presence of detectable subclonal driver mutations was associated with shorter time to relapse and retreatment (P=.04). In the full group of 149 samples, subclonal drivers were associated with shorter times from diagnosis to first therapy (P=.001) and between sample collection and treatment (P<.001). Subclonal drivers are independent risk factors for earlier retreatment and are associated with shorter duration of remission.


Table 2

The ASH 2012 CLL educational program entitled Chronic Lymphocytic Leukemia: Can New Prognostic Factors Guide New Therapeutic Approaches? included 3 presentations: “Implications of New Prognostic Markers in Chronic Lymphocytic Leukemia,”18 “Emerging Role of Kinase-Targeted Strategies in Chronic Lymphocytic Leukemia,”19 and “A Look Into the Future: Can Minimal Residual Disease Guide Therapy and Predict Prognosis in Chronic Lymphocytic Leukemia?”20 Full texts of each of these presentations are available from the American Society of Hematology.18-20

Alessandra Tedeschi, MD, Niguarda Ca’ Granda Hospital, Milan, Italy, presented the poster “Final Report of Bendamustine and Alemtuzumab (BEN CAM) Combination in Relapsed and Refractory Chronic Lymphocytic Leukemia.”21 A single-arm dose-escalation study determined the maximum tolerated dose (MTD) of 4 weekly courses of BEN CAM in patients with relapsed/refractory CLL. MTD was defined as 70 mg/m2 BEN and 30 mg CAM in the 12 patients in phase 1; 50 patients were enrolled. ORR was 68% at a median follow-up of about 16 months. Serious AEs included hematologic toxicity and manageable
myelosuppression.

Jan A. Burger, MD, PhD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, gave an oral presentation at ASH, “The Btk Inhibitor Ibrutinib (PCI-32765) in Combination With Rituximab Is Well Tolerated and Displays Profound Activity in High-Risk Chronic Lymphocytic Leukemia (CLL) Patients.”22 Ibrutinib is a Bruton’s tyrosine kinase (Btk) inhibitor that blocks B-cell receptor signaling. In this phase 2 study, 40 patients with high-risk CLL received combination ibrutinib plus rituximab, followed by reduced-dose ibrutinib plus rituximab, followed by ibrutinib monotherapy. High-risk disease was defined by the presence of del(17p) or TP53 mutations in treated or untreated patients, del(11q) in patients with relapsed CLL, or remission of fewer than 36 months following first-line chemoimmunotherapy. At a median follow-up of 4 months, 38 patients continued on therapy without disease progression, 1 patient had died from an unrelated infectious complication, and 1 patient withdrew from the study before starting therapy. Of the 20 patients who were evaluable for early response assessment at 3 months, 17 had a partial remission (PR) and 3 had PR with persistent lymphocytosis. ORR was 85%. AEs included neutropenia, diarrhea, bone pain, fatigue, and pneumonia. Evaluable patients reported improved health and QOL after 3 cycles of treatment. Burger concluded by emphasizing the need for further development of ibrutinib for patients with CLL, who have few other treatment options.

Chronic Myeloid Leukemia and Ph+ ALL

Dr Jorge E. Cortes, Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, Texas, gave an oral presentation, “A Pivotal Phase 2 Trial of Ponatinib in Patients With Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Resistant or Intolerant to Dasatinib or Nilotinib, or With the T315I BCR-ABL Mutation: 12-Month Follow-up of the PACE Trial.”23 The PACE trial included 449 patients with CML or with Ph+ acute lymphocytic leukemia (Ph+ ALL). All patients had been heavily pretreated, receiving a median of 3 tyrosine kinase inhibitors (TKIs). Patients were stratified according to disease phase, and primary end points were defined for each disease phase. Of patients with chronic-phase (CP) CML (n=270), 55% had a major cytogenetic response within 12 months of treatment, and 91% were estimated to have a sustained response at 12 months. A complete cytogenetic response was seen in 46% of patients with CP CML, and those with a shorter duration of disease or fewer prior TKIs had a higher response rate. Of patients with accelerated-phase (AP) CML (n=85), 58% reached the primary end point of major hematologic response within 6 months of treatment; 34% of patients with blast-phase (BP) CML or Ph+ ALL (n=94) also reached this end point. Responses were not affected by the presence of the T315I mutation. Ponatinib was generally well tolerated. AEs included rash, abdominal pain, headache, dry skin, constipation, fatigue, pyrexia, nausea, arthralgia, hypertension, pancreatitis, elevated pancreatic enzymes, and myelosuppression. Shortly after the ASH meeting, ponatinib was approved for the treatment of adult patients with CP, AP, or BP CML or Ph+ ALL that is resistant to or intolerant of prior TKI therapy. A phase 3 trial is ongoing comparing ponatinib with imatinib in patients with newly diagnosed CP CML.

Chronic Myelogenous Leukemia

Joseph Jurcic, MD, Memorial Sloan-Kettering Cancer Center, New York City, moderated a sponsored symposium entitled Clinical Dialogues in CML: Current Paradigms and Emerging Strategies. Jurcic pointed out that new NCCN guidelines for CML, version 3.2013, were issued shortly before the symposium, and all speakers referred to them.24 Since then, ponatinib has also been approved for CML. Javier Pinilla-Ibarz, MD, PhD, H. Lee Moffitt Cancer Center, Tampa, Florida, led a case-based roundtable discussion, “Newly Diagnosed CML – Addressing Primary Resistance.” The recent NCCN guidelines have new criteria for failure to respond to TKI therapy. After establishing nonresponse to imatinib, mutational analysis should guide second-line therapy. Thomas G. Martin III, MD, University of California, San Francisco, California, led a discussion, “Newly Diagnosed Chronic Phase CML – Challenges of Identifying Non-Adherence to Therapy.” Universal assessment of adherence in patients can distinguish nonresponse or relapse from nonadherence. Nonadherence is not all-or-nothing and has patient-
related, healthcare system–related, and treatment-
related components. Approaches include electronic medication caps and allowing patients to try different regimens for several months at a time. Mark L. Heaney, MD, PhD, Memorial Sloan-Kettering Cancer Center, New York City, led a discussion, “Strategies in the Management of Secondary Resistance and in Chronic Phase CML.” In addition to second-line TKI alternatives, the recently approved omacetaxine is another option. In the subsequent Q&A session, the panelists agreed that they prefer second-generation TKIs to imatinib. Pinilla-Ibarz led a discussion, “Management of the Accelerated Phase CML Patient,” referring to the NCCN guidelines, and recommending omacetaxine after TKI failure, taking mutational analysis into consideration. Ponatinib and hematopoietic stem cell transplantation (SCT) should also be considered. Heany also led the discussion, “Management of the Blast Crisis CML Patient.” NCCN treatment guidelines are based on the type of blast cells and generally include the option of clinical trials, acute myeloid leukemia (AML)- or ALL-type induction, and TKI followed by allogeneic SCT. Jurcic presented “Addressing Clinical Barriers to Overcoming Resistance, Treatment Failure – Emerging Therapeutics,” noting the recently approved options of bosutinib, omacetaxine, and, since the meeting, ponatinib, and agents in trials, including rebastinib and hedgehog pathway inhibitors.

Of note, there were 2 poster presentations at ASH on omacetaxine mepesuccinate in CML: “Blast Phase Chronic Myeloid Leukemia: A Pooled Analysis of Subcutaneous Omacetaxine Mepesuccinate in Treatment-Resistant Patients,” presented by H. Jean Khoury, MD, Winship Cancer Institute of Emory University, Atlanta, Georgia,25 and “Long-Term Follow-up of Ongoing Patients in 2 Studies of Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia,” presented by Hagop M. Kantarjian, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas.26 Subcutaneous omacetaxine mepesuccinate (omacetaxine) is a first-in-class cephalotaxine that inhibits protein synthesis independent of direct binding of Bcr-Abl, reduces levels of multiple oncoproteins, and induces apoptosis in leukemic stem cells. Both posters reported on subanalyses of patients with different disease subtypes in the CML-202 and CML-203 studies in patients with TKI-resistant CML. In 44 patients with BP CML, hematologic improvement was seen in 13% of patients, and 2 patients had responses lasting >1 year. Grade 3/4 AEs were mostly hematologic; death due to disease progression occurred in 57% of patients. The authors concluded that omacetaxine in combination with chemotherapy and SCT in otherwise ineligible patients should be studied.25 Of the 108 patients with CP CML and 51 with AP CML, 9 and 2 patients continue to receive treatment after a median 35 and 22 cycles, respectively. All 9 patients with CP CML maintained a complete hematologic response (CHR) and 7 had a major cytogenetic response, including 6 complete responses (CRs). One patient with CP CML had a durable CHR. Grade 3/4 AEs were mostly hematologic and consistent with the known safety profile of
omacetaxine.26

Non-Hodgkin Lymphoma

John M. Burke, MD, Rocky Mountain Cancer Centers, Aurora, Colorado, gave an oral presentation, “Differences in Quality of Life Between Bendamustine Plus Rituximab Compared With Standard First-Line Treatments in Patients With Previously Untreated Advanced Indolent Non-Hodgkin’s Lymphoma or Mantle Cell Lymphoma.”27 The primary objective was to compare the response rate for bendamustine plus rituximab (BR) with the standard regimens for indolent non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL): rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). Treatment-naive patients with indolent NHL or MCL were randomly assigned to either BR or standard R-CHOP/R-CVP. The QLQ-C30 30-question survey was used to measure global health status (GHS) and QOL prior to start of treatment, after cycles 1, 3, 6, 8, and at the end of treatment. Patients treated with BR had a significantly higher mean change in GHS/QOL from baseline to final visit. Improvement in cognitive function was reported in the BR group after cycles 1 and 3, and improvement in physical function was reported after cycle 6.

Acute Myeloid Leukemia

Dr Johan Maertens, Department of Hematology, University Hospital Gasthuisberg Leuven, Leuven, Belgium, was the first author of the oral presentation, “Phase I/II Study of Volasertib (BI 6727), an Intravenous Polo-Like Kinase (Plk) Inhibitor, in Patients With Acute Myeloid Leukemia (AML): Results From the Randomized Phase II Part for Volasertib in Combination With Low-Dose Cytarabine (LDAC) Versus LDAC Monotherapy in Patients With Previously Untreated AML Ineligible for Intensive Treatment.”28 This presentation reported preliminary results from the phase 2 portion of a study comparing volasertib in combination with LDAC versus LDAC alone in patients with AML ineligible for intensive remission induction therapy (high-dose chemotherapy over a short time period). These patients tend to be older and have a poor prognosis. Volasertib is an inhibitor of polo-like kinase 1, which is involved in spindle assembly during mitosis. This open-label trial randomly assigned 87 patients (median age, 75-76 years) to volasertib in combination with LDAC (n=42) or LDAC alone (n=45). Objective responses (CR or CR with incomplete blood count recovery) were observed in 31% of patients treated with the combination of volasertib plus LDAC compared with 13.3% of the patients treated with LDAC alone (P=.0523). The median time to remission was 71 days (range, 29-158 days) and 64 days (range, 30-125 days), respectively. In patients treated with the combination of volasertib plus LDAC, the median event-free survival (EFS) was ~5.6 months compared with ~2.3 months in patients treated with LDAC alone (P=.0237). Follow-up for OS is ongoing. Patients in the volasertib plus LDAC treatment arm experienced an increased rate of AEs compared with those in the LDAC monotherapy arm. Grade 5 AEs in the volasertib plus LDAC group included 5% each of infections and febrile neutropenia and 7% respiratory events. Grade 3/4 AEs included infections, febrile neutropenia, metabolic/nutritional events, respiratory events, and gastrointestinal events. In the LDAC arm, 9% grade 5 infections were seen; grade 3/4 events included febrile neutropenia and infections. Based on the phase 2 results of this trial, a phase 3 trial of volasertib will compare LDAC alone with LDAC plus volasertib in 660 previously untreated patients with AML aged 65 years and older who are ineligible for high-intensity therapy.

Acute Promyelocytic Leukemia

Francesco Lo-Coco, MD, University Tor Vergata, Rome, Italy, presented “ATRA and Arsenic Trioxide (ATO) Versus ATRA and Idarubicin (AIDA) for Newly Diagnosed, Non High-Risk Acute Promyelocytic Leukemia (APL): Results of the Phase III, Prospective, Randomized, Intergroup APL0406 Study by the
Italian-German Cooperative Groups Gimema-SAL- AMLSG” during the plenary session at ASH.29 This phase 3 trial randomly assigned adults with newly diagnosed, genetically confirmed, non–high-risk APL to ATO + ATRA (ATO arm, n=75) or ATO + idarubicin induction followed by ATRA + anthracycline consolidation and low-dose chemotherapy, followed by ATRA maintenance (chemo arm, n=80). In each arm, 75 patients were evaluable. Hematologic toxicities were significantly higher in the chemo arm during induction and consolidation; other toxicities were manageable. After a median follow-up of 34.3 months, disease-free survival for the ATO arm was 97% versus 90% for the chemo arm; the cumulative incidence of relapse was 1.5% for the ATO arm versus 5.6% for the chemo arm (differences not significant). OS was 98.7% versus 91.1% for ATO and chemo, respectively; EFS was 97% for ATO and 85.6% for chemo (these differences are significant). The study authors concluded that ATO + ATRA is not inferior to ATRA + chemo for 2-year EFS in patients with low- to intermediate-risk APL and may emerge as a chemotherapy-free option in this patient population.

Multiple Myeloma

Dr Heinz Ludwig, Wilhelminen Hospital, Vienna, Austria, gave an oral presentation at ASH entitled “Treatment With Bendamustine-Bortezomib-Dexamethasone (BBD) in Relapsed/Refractory Multiple Myeloma Shows Significant Activity and Is Well Tolerated.”30 In this phase 2 trial, patients with relapsed/refractory multiple myeloma (MM) received 70 mg/m2 bendamustine, standard-dose bortezomib, and low-dose dexamethasone. Of 79 patients enrolled (ITT [intent-to-treat] population), 71 were evaluable for response. After a median follow-up of 13.7 months, the ORR in the evaluable population was 67.6%, and 60% in the ITT population. The PFS was 9.7 months, and the 2-year OS was estimated to be 60%. Prior bortezomib did not affect PFS, but for patients with no prior lenalidomide PFS was significantly longer at 12.8 months versus 8 months for those with prior lenali­domide. Adverse cytogenetics was not associated with decreased PFS or OS. Hematologic toxicities were manageable. Nonhematologic toxicities included polyneuropathy (PNP; 49% grade 1/2, 5% grade 3, 1% grade 4). FACT/GOG-NTX 4 was used for self-
assessment for PNP at cycle 1. There was an increase in self-reported severe PNP over time. Investigators assessing patients for PNP reported less severe PNP than did the patients. Ludwig concluded that BBD is a valuable choice for patients with previously treated relapsed/refractory MM.

Antonio Palumbo, MD, Division of Hematology, University of Torino, Torino, Italy, presented “Overall Survival Benefit for Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide (VMPT-VT) Versus Bortez­omib-Melphalan-Prednisone (VMP) in Newly Diagnosed Multiple Myeloma Patients.”31 Palumbo called the 4-drug combination VMPT the “best experimental therapy,” which was compared in this study to the 3-drug combination VMP, which he characterized as the “best standard of care.” Previously published results of this phase 3 study in 511 elderly patients showed that VMPT followed by maintenance therapy with VT (n=254) was superior to VMP (n=257) for response rates, PFS, and time to next treatment. Palumbo presented an update of the survival analysis after 4 years of follow-up. OS was not reached in the VMPT-VT group and was 58.2 months for the VMP group. Patients receiving VMPT-VT had a 26% reduced risk of death, with patients younger than 75 years benefiting more than older patients. Patients who had CR after induction also had a reduced risk of death with the 4-drug combination versus the 3-drug combination. Survival was not significantly affected by high-risk cytogenetic features. The median duration of VT maintenance was approximately 2 years and was associated with 7% grade 3/4 peripheral neuropathy, 5% grade 3/4 hematologic toxicity, and 3% grade 3/4 infection, with 12% of patients discontinuing due to AEs. Second primary malignancies were reported in 7 of 254 patients in the VMPT-VT group and 7 of 257 patients in the VMP group, which is similar to the background incidence rates in the general population of similar age to the patient population in this study. Palumbo concluded that the 4-drug combination of VMPT followed by VT maintenance should be considered a new standard of care for patients aged 67 to 75 years.

References
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22. Burger JA, Keating MJ, Wierda WG, et al. The Btk inhibitor ibrutinib (PCI-32765) in combination with rituximab is well tolerated and displays profound activity in high-risk chronic lymphocytic leukemia (CLL) patients. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 187.
23. Cortes JE, Kim D-W, Pinilla-Ibarz J, et al. A pivotal phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant or intolerant to dasatinib or nilotinib, or with the T315I BCR-ABL mutation: 12-month follow-up of the PACE trial. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 163.
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26. Kantarjian HM, Lipton JH, Baccarani M, et al. Long-term follow-up of ongoing patients in 2 studies of omacetaxine mepesuccinate for chronic myeloid leukemia. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 2787.
27. Burke JM, Van der Jagt RH, Kahl BS, et al. Differences in quality of life between bendamustine plus rituximab compared with standard first-line treatments in patients with previously untreated advanced indolent non-Hodgkin’s lymphoma or mantle cell lymphoma. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 155.
28. Maertens J, Lübbert M, Fiedler W, et al. Phase I/II study of volasertib (BI 6727), an intravenous polo-like kinase (Plk) inhibitor, in patients with acute myeloid leukemia (AML): results from the randomized phase II part for volasertib in combination with low-dose cytarabine (LDAC) versus LDAC monotherapy in patients with previously untreated AML ineligible for intensive treatment. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 411.
29. Lo-Coco F, Avvisati G, Orlando SM, et al. ATRA and arsenic trioxide (ATO) versus ATRA and idarubicin (AIDA) for newly diagnosed, non high-risk acute promyelocytic leukemia (APL): results of the phase III, prospective, randomized, intergroup APL0406 study by the Italian-German cooperative groups Gimema-SAL-AMLSG. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 6.
30. Ludwig H, Kasparu H, Greil R, et al. Treatment with bendamustine-bortezomib-dexamethasone (BBD) in relapsed/refractory multiple myeloma shows significant activity and is well tolerated. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 943.
31. Palumbo A, Bringhen S, Rossi D, et al. Overall survival benefit for bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in newly diagnosed multiple myeloma patients. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 200.

Last modified: May 21, 2015