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18th Annual International Congress on Hematologic Malignancies Resources

18th Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and Myeloma


Resources

18th Annual International Congress on Hematologic Malignancies®: Meeting-in-a-Box
The Meeting-in-a-Box components are designed for you to share the information with colleagues, fellows, and other healthcare professionals.

PER Pulse™ Recap
Three PER Pulse™ Recaps present key topics from the 18th Annual International Congress on Hematologic Malignancies®, which was held on February 14 - 15, 2014.





PER Meeting in a Box
Multiple Myeloma
Presentation Title Faculty Discussion Questions
High-risk smoldering myeloma - what should we do? Ola Landgren, MD How do you stratify risk in your patients with smoldering  multiple myeloma (SMM)? What are the goals of early treatment for SMM? In the past 25 years, what therapies have been investigated for the treatment of monoclonal gammopathy of undetermined significance, SMM, and asymptomatic/indolent multiple myeloma (MM)?
Landscape of treatment for relapsed multiple myeloma James Berenson, MD Which therapeutic strategies do you use most often in patients with relapsed/refractory MM and why? What are the main criteria you use to establish a treatment plan for a patient with relapsed/refractory MM? How do you determine which patients with relapsed/refractory MM can be watched and which patients require treatment? How do you treat patients with relapsed/refractory MM who have extramedullary disease?
Leukemia #1 (Chronic Myelogenous Leukemia/Myeloproliferative Neoplasms)
Which TKI should be used as initial therapy for patients in chronic phase, considering the longer term toxicities recently described with "second-generation" TKIs? Charles Schiffer, MD   How do second-generation tyrosine kinase inhibitors (TKIs) compare with imatinib in terms of overall and progression-free survival when used as initial therapy in patients with chronic-phase chronic myelogenous leukemia (CML)? Do you regularly use the Sokal score to help determine initial therapy in a patient with chronic-phase CML? How does the cost of imatinib, compared with that of approved second-generation TKIs, factor into the discussion you have with your patients regarding treatment?
Should therapy be switched in patients in chronic phase who fail to achieve a transcript level below 10% (IS) after 3 months of treatment with imatinib? Harry Erba, MD, PhD Do you regularly assess for interference with drug absorption in a patient with chronic-phase CML who has a BCR-ABL transcript level >10% at 3 months? How important is molecular response at 3 months in driving subsequent treatment decision making in your patients with chronic-phase CML?
Is there evidence for the use of prophylactic antibiotics and antifungal agents during the treatment of acute leukemia? Susan Seo, MD What are the main advantages and disadvantages of using antimicrobial prophylaxis in patients with acute leukemia? What are the main risk factors for infection in patients with acute leukemia, and how common are they in your patients with acute leukemia?
Lymphoma #1
Lymphoma classification and impact of genomics Randy Gascoyne, MD What therapeutic agents may selectively benefit the germinal center B-cell (GCB) vs activated B-cell-like (ABC) subtypes of diffuse large B-cell lymphoma (DLBCL)? What is the potential for targeting EZH2 mutations in follicular lymphoma (FL) and GCB DLBCL? How does awareness of mutational status influence your treatment decision making?
Is cell of origin important in the primary management of DLBCL? John P. Leonard, MD What factors pertaining to the assay, patient population, and drug activity should be considered in targeting a DLBCL subset based on cell of origin in the frontline setting?
Beyond high-dose therapy – management of relapsed/refractory DLBCL Anas Younes, MD What strategies can be used to improve treatment outcome in transplant-eligible and transplant-ineligible patients with DLBCL after failure with R-CHOP induction therapy?
CNS lymphoma - state of the art Lisa DeAngelis, MD What is your current standard of care in patients with primary CNS lymphoma? How do you assess your patients with primary CNS lymphoma for neurotoxicity and cognitive impairment? Which patients with primary CNS lymphoma treated with combined modality therapy have the greatest risk of leukoencephalopathy?  
Chronic Lymphocytic Leukemia
Receptor pathways to target for CLL therapy Jennifer Brown, MD What pattern of response is observed in terms of lymph node activity and lymphocyte redistribution when the BCR pathway is inhibited in chronic lymphocytic leukemia (CLL)?
Anti-apoptotic protein as therapeutic target in CLL Thomas Kipps, MD, PhD Why are anti-apoptotic proteins, such as Bcl-2, good targets for CLL therapy? What are some Bcl-2 inhibitors currently under investigation in CLL?
Management of CLL in elderly patients Alessandra Ferrajoli, MD What proportion of your patients with CLL are age 65 years or older, and how does their management differ from that in patients younger than age 65 years? How does the presence and severity of comorbidities in elderly patients with CLL affect your treatment decision making? In addition to treatment for CLL, what general health maintenance measures do you implement in elderly patients?
Emerging important gene mutations in CLL Catherine J. Wu, MD How does the awareness of new genetic markers in CLL affect prognosis and treatment decision making?
Leukemia #2 (Acute Leukemia/Myelodysplastic Syndromes)
Who should be transplanted for ALL in first remission? What is the role of minimal residual disease assessment? Mark R. Litzow, MD How often do you use a pediatric approach (ie, higher doses of nonmyelosuppressive agents than those in an adult-based regimen) in young adults with acute lymphoblastic leukemia (ALL)? What risk factors do you consider in deciding whether a patient with ALL in first remission is a candidate for transplantation vs chemotherapy? Do factors other than patient age affect your decision to use reducedintensity conditioning vs myeloablative conditioning?
Should patients with refractory anemia with excess blasts or those with oligoblastic AML receive induction therapy prior to allogeneic transplantation? Harry Erba, MD, PhD What are the practical benefits of pre-allogeneic hematopoietic stem cell transplantation (HSCT) chemotherapy in patients with myelodysplastic syndrome (MDS) or early-relapse acute myeloid leukemia (AML)? What risk factors have been shown to adversely affect overall survival in patients who underwent transplantation for AML in relapse or primary induction failure?
Is there a role for iron chelation therapy in patients with MDS? Virginia Klimek, MD What is the rationale for administering iron chelation therapy to patients with MDS? Which patients with MDS would be most likely to benefit from iron chelation therapy? How is iron overload measured? What are the consequences of iron-mediated toxicity?
How can I manage acute promyelocytic leukemia? Martin Tallman, MD What are the main causes of induction mortality in acute promyelocytic leukemia (APL)? What is the optimal treatment in patients with high-risk APL? What is the benefit of maintenance therapy in patients with APL?
Lymphoma #2
FL in situ vs partial involvement by FL, MCL in situ Randy Gascoyne, MD How is follicular lymphoma in situ (FLIS) distinguished from partial involvement by FL? How is FLIS typically staged and managed?
Mantle cell lymphoma - new options for therapy Andre Goy, MD What are the main goals of using dose-intensive strategies as frontline therapy in younger (relatively fit) patients with mantle cell lymphoma (MCL)? What are the main disadvantages of using high-dose frontline therapy, such as R (rituximab)-hyper-CVAD, in elderly patients with MCL?
Current and future of high-dose therapy in mantle cell lymphoma Issa F. Khouri, MD What do the data show regarding the correlation between serum rituximab concentrations and response in patients with MCL? What treatment strategies would you consider in a patient with MCL who had an elevated Ki-67 level (ie, Ki-67 >30%)?
Management of non-follicular indolent lymphoma Andrew Zelenetz, MD, PhD How effective is splenectomy in the treatment of splenic marginal zone lymphoma? In which patients with splenic marginal zone lymphoma should treatment with rituximab monotherapy or rituximab in combination with cladribine be considered? Which translocation is associated with antibiotic resistance in gastric mucosa-associated lymphoid tissue (MALT) lymphoma? What is the optimal approach to persistent minimal residual gastric MALT lymphoma?
Hodgkin Lymphoma
Molecular prognostication in HL Randy Gascoyne, MD How does the microenvironment of classic Hodgkin lymphoma (HL) differ from that of other B-cell lymphomas? What is your opinion regarding the use of ABVD vs escalated BEACOPP to treat patients with advanced-stage classical HL? Do you anticipate that gene expression profiling will soon be used routinely in clinical practice?
Debate: Early-stage HL - can radiation be eliminated? NO Joachim Yahalom, MD What are the disadvantages associated with the use of chemotherapy alone in patients with early-stage HL? How have the volume and dose of radiation administered to women with early-stage HL changed in the past 30 years, and what effect have the changes had on outcome? Is chemotherapy alone a reasonable treatment strategy in young women with early-stage HL who would require radiation exposure of the breast?
Debate: Early-stage HL - can radiation be eliminated? YES John Radford, MD What late treatment-related effects could potentially occur from the administration of chemotherapy, radiation therapy, or combined modality therapy in patients with early-stage HL? In planning a treatment strategy for a patient with early-stage HL, do you think that achieving maximum initial disease control should always be viewed within the context of potential late treatment-related toxicity? What clinical characteristics can be used to stratify risk in patients with early-stage HL for the purpose of treatment decision making?
PET-directed therapy in HL Craig H. Moskowitz, MD Given that PET/computed tomography upstages 15% to 25% of patients with HL, are you concerned about the potential for overtreatment? What is the most important determinant for choice of first-line therapy in patients with HL?
New Directions in Hematologic Malignancies
Cellular therapy with chimeric antigen receptors in lymphoid malignancies Renier Brentjens, MD, PhD What are the potential advantages of using chimeric antigen receptors (CARs) in lymphoid malignancies? What do the data show regarding the efficacy of CD19-targeted CAR T cells in patients with relapsed B-cell ALL?
B-cell receptor pathway-directed therapy in lymphoid malignancies Anas Younes, MD Which kinases does ibrutinib inhibit in the Tec family? What mutations have been shown to predict resistance to ibrutinib in patients with ABC DLBCL?
Bone health in hematologic malignancies James Berenson, MD How do you manage tumor-related vertebral compression fractures in your patients with hematologic malignancies? What are the potential side effects of external-beam radiotherapy in patients with bone metastases? Do you regularly use bisphosphonates to inhibit bone loss in your patients with hematologic malignancies? What are the main side effects associated with oral and intravenous bisphosphonates? What measures can be implemented to minimize the risk of osteonecrosis of the jaw in patients with hematologic malignancies receiving intravenous bisphosphonates? What measures can be implemented to reduce the development of skeletal complications in patients with hematologic malignancies?  
Do hypomethylating agents "really work" via an epigenetic mechanism? Ari Melnick, MD What is currently known about the mechanisms of aberrant hypermethylation (which leads to the silencing of genes) and aberrant hypomethylation (which leads to the activation of genes) in AML and ALL? How are DNA methylation heterogeneity and DNA methylation variability scores linked to clinical outcome? What are the challenges in interpreting cytosine analog DNMTi studies?




PER Pulse™ Recap

PER Pulse™ Recap
Medical Writer: Kathleen Wildasin


1 of 3
PER Pulse Recap
18th Annual International Congress on a Hematologic Malignancies®
Is There Evidence For The Use Of Prophylactic Antibiotics and Antifungal Agents During the Treatment of Acute Leukemia?

The 18th Annual International Congress on Hematologic Malignancies®, which was held February 14-15, 2014, in New York City, brought together experts from across the country and beyond to discuss and debate current issues pertaining to the management of leukemias, lymphomas, and myeloma. This first of 3 PER Pulse™ Recaps focuses on the use of antimicrobial prophylaxis in patients with acute leukemia, as presented by Dr. Susan Seo.

Dr. Seo began her presentation by discussing the advantages and disadvantages of antimicrobial prophylaxis in patients with acute leukemia, and then focused on the risk factors associated with infection in cancer patients, clinical trial data pertaining to antibiotic and antifungal prophylaxis, and current antimicrobial prophylaxis guidelines for patients with acute leukemia. The following paragraphs summarize the main points of Dr. Seo’s presentation.

The purpose of using antimicrobial prophylaxis in patients with acute leukemia is to reduce infection and mortality; however, disadvantages include increased costs, added pill burden, toxicity, and the potential for resistance. The use of antimicrobial prophylaxis is more appropriate in patients at high risk of infection rather than universally.

Neutropenia is an important risk factor for infection in patients with acute leukemia. Specifically, the risk of infection increases as the neutrophil count decreases, especially when the absolute neutrophil count is ≤100 cells/mm3 (ie, profound neutropenia). Other risk factors include the duration of neutropenia, malignancy status (active or in remission), and treatment type. Patients with solid tumors who receive standard chemotherapy are at low risk of infection, with an anticipated neutropenia duration of <7 days; patients with lymphoma, multiple myeloma (MM), and chronic lymphocytic leukemia (CLL) and those who receive autologous hematopoietic stem cell transplantation (HSCT) are at intermediate risk, with an anticipated neutropenia duration of 7-10 days; and patients with acute leukemia and those who receive allogeneic SCT (including cord blood) are at high risk, with an anticipated neutropenia duration of >10 days. Alemtuzumab therapy and graft-versus-host disease and its therapy are also associated with a high risk of infection.

Since the 1980s, numerous randomized trials have shown a reduction in febrile events and infection with the use of antibiotic prophylaxis; however, the lack of a clear mortality benefit and concerns about antibiotic resistance have driven the argument against routine usage. In 2005, however, new evidence came to light: A meta-analysis of 95 randomized controlled trials (1973-2004), 52 of which addressed fluoroquinolone prophylaxis, showed that antibiotic prophylaxis significantly reduced all-cause mortality in afebrile neutropenic patients with hematologic malignancies compared with placebo or no treatment (relative risk, 0.67 [95% CI, 0.55-0.81]). It is important to note, however, that the study had several limitations, including potential publication bias (studies with negative results may not have been published), lack of data in patients with solid tumors, lack of data on resistance, and/or inadequate length of follow-up. In 2012, the authors of the meta-analysis updated their data to include 109 additional trials (1973-2010) and reported similar all-cause mortality findings.

At present, the National Comprehensive Cancer Network (NCCN), Infectious Diseases Society of America (IDSA), and European Conference on Infections in Leukemia (ECIL) recommend considering fluoroquinolone prophylaxis in high-risk patients (ie, those with an anticipated neutropenia duration of >7 days). In addition, the ECIL recommends quinolone prophylaxis specifically in patients with acute leukemia.

Antifungal prophylaxis for all patients with neutropenia is not appropriate, as drug-related toxicity and the emergence of resistance could outweigh the benefits in those who are at low risk of infection. In a retrospective multicenter cohort study conducted in Italy (1999-2003) in 11,802 patients with hematologic malignancies, the overall incidence of proven or probable invasive fungal infections (IFIs) was 4.6%, with rates ranging from 0.5% in patients with MM to 12% in those with acute myelogenous leukemia (AML). Mortality attributed to IFIs was 39%.

Several randomized multicenter studies (1999-2006) have investigated the use of antifungal prophylaxis (eg, fluconazole, itraconazole) generally administered within 72 hours of chemotherapy in patients with hematologic malignancies, including those with acute leukemias. The findings were mixed in terms of reduction in IFIs and attributable/overall mortality, perhaps because the studies were underpowered to detect significant differences.

In 2007, data from a randomized multicenter study conducted in patients with AML (86%) and myelodysplastic syndromes (MDS; 14%) showed that the incidence of IFIs was 2.3% and 8.4% in those receiving induction chemotherapy with posaconazole versus fluconazole or itraconazole, respectively; attributable mortality was 1.6% and 5.4%, respectively; and all-cause mortality was 14.5% and 21.5%, respectively. At present, NCCN, IDSA, and ECIL recommend considering posaconazole prophylaxis in patients undergoing induction chemotherapy for acute leukemia or MDS.

In conclusion, patients with acute leukemia with anticipated neutropenia duration of >7 days due to intensive chemotherapy are considered to be at high risk of infection and are reasonable candidates for antibiotic and antifungal prophylactic therapy. If antimicrobial prophylaxis is implemented at a center, monitoring for resistance is recommended.


2 of 3
PER Pulse Recap
18th Annual International Congress on Hematologic Malignancies®
New Therapy Options in Mantle Cell Lymphoma

The 18th Annual International Congress on Hematologic Malignancies®, which was held February 14-15, 2014, in New York City, brought together experts from across the country and beyond to discuss and debate current issues pertaining to the management of leukemias, lymphomas, and myeloma. This second of 3 PER Pulse™ Recaps focuses on new therapy options in mantle cell lymphoma (MCL), as presented by Dr. Andre Goy.

Dr. Goy began his presentation with an overview of MCL, and then discussed frontline therapy in fit versus nonfit or elderly patients, novel agents in the relapsed setting, and emerging biologic agents. The following paragraphs summarize the main points of Dr. Goy’s presentation.

In the past three decades, overall survival (OS) in patients with MCL (with the exception of blastoid variants) has increased from 2.5 to 5 years, and the use of intensive approaches-especially high-dose Ara-C (cytarabine)-has led to progression-free survival (PFS) rates that exceed 5 years. Yet, the incidence of relapse and chemoresistance remains high. New treatment strategies to improve outcomes are clearly needed.

The MCL treatment landscape has changed markedly in recent years. Several agents have been approved for use in the United States and Europe, and numerous others are under investigation in the frontline, maintenance, and relapsed settings. High-dose regimens are being evaluated in younger, fit patients with MCL.

In the frontline setting, aggressive regimens have been associated with longer PFS rates than have R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens in younger patients. For example, in a study in 167 patients with MCL who were younger than age 65 years, PFS at 3 years with R-CHOP versus dose-intensive strategies was 18% and 56% to 58%, respectively. In another study-this one in 420 patients with MCL who were younger than age 65 years-treatment with alternating R-CHOP and R-DHAP (rituximab, cytarabine, cisplatin, and dexamethasone) followed by a high-dose Ara-C-containing myeloablative regimen yielded longer time to treatment failure, remission duration, and OS than did treatment with R-CHOP followed by myeloablative radiochemotherapy and autologous stem cell transplantation. Despite the benefits of high-dose frontline therapy in younger patients with MCL, those with high versus low scores on the Mantle Cell International Prognostic Index still do poorly, and some patients experience late relapses. The current goals of using dose-intensive strategies in this patient population include achieving early and deeper responses and preventing relapses.

High-dose frontline therapy cannot be administered in most elderly patients with MCL. The use of R-hyper-CVAD (rituximab in combination with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with rituximab in combination with high-dose methotrexate-cytarabine (R-MA) has been associated with delays, dose reduction, and toxicity in patients with MCL older than age 65 years. In contrast, a modified R-hyper-CVAD regimen (ie, traditional hyper-CVAD without methotrexate or cytarabine) used in 22 untreated patients with MCL (median age, 63 years) has been associated with an objective response rate (ORR) of 77% and a complete response (CR) rate of 64%, with mainly hematologic toxicity. Additionally, combination therapy using bortezomib or bendamustine has also shown promise as frontline therapy in elderly patients with MCL.

Results of the first randomized trial in elderly (age >60 years) patients with MCL were published in 2012. In the trial, 560 patients with stage II to IV MCL were randomly assigned to either 8 cycles of R-CHOP every 21 days or 6 cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days; responders underwent maintenance therapy with rituximab or interferon-alfa until disease progression. The 4-year OS rate was significantly shorter with R-FC than R-CHOP (47% vs 62%, respectively; P = .005). Of the patients who responded to R-CHOP, maintenance therapy with rituximab versus interferon-alfa significantly improved 4-year OS (87% vs 63%, respectively; P = .005).

Clinical trial participation should be considered in patients with relapsed/refractory MCL. Many monotherapy and combination therapy strategies using proteasome inhibitors (bortezomib and carfilzomib), the mTOR inhibitor temsirolimus, and the immunomodulatory agent lenalidomide have already been investigated or are currently undergoing investigation in clinical trials. For example, in a study in 16 patients with relapsed/refractory MCL, patients treated with bortezomib in combination with dexamethasone and rituximab achieved an ORR of 82%, with 44% of patients achieving a CR. In another trial-this — one in 44 patients with relapsed/refractory MCL treated with lenalidomide in combination with rituximab  —  ORR was 57%, with 36% of patients achieving a CR; median duration of response was 18.9 months. Another study reported ORR and CR of 59% and 19%, respectively, in 69 assessable patients with relapsed/refractory MCL who were treated with temsirolimus and rituximab; in rituximab-refractory patients (n=21), the rates were 52% and 24%, respectively.

Emerging new biologic agents, such as idelalisib (formerly CAL-101 and GS-1101) and Bruton’s tyrosine kinase, are also being studied in the relapsed/refractory MCL setting. ABT-199, an oral second-generation BH3 mimetic that inhibits BCL2, is being investigated in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), including those with MCL. In a phase I study in patients with NHL, 100% of patients with MCL (n=8) treated with ABT-199 achieved a partial response.


3 of 3
PER Pulse Recap
18th Annual International Congress on Hematologic Malignancies®
High-Risk Smoldering Myeloma - What Should We Do?

The 18th Annual International Congress on Hematologic Malignancies®, which was held February 14-15, 2014, in New York City, brought together experts from across the country and beyond to discuss and debate current issues pertaining to the management of leukemias, lymphomas, and myeloma. This third of 3 PER Pulse™ Recaps focuses on the management of patients with high-risk smoldering multiple myeloma (SMM), as presented by Dr. Ola Landgren.

Dr. Landgren began his presentation by stating the International Myeloma Working Group (IMWG) definition of SMM, and went on to discuss clinical trial data on the risk of progression from SMM to symptomatic disease, risk stratification models, treatment recommendations and goals, and therapies used in the management of SMM. The following paragraphs summarize the main points of Dr. Landgren’s presentation.

According to the IMWG, SMM is a plasma cell disorder that meets two criteria: (1) a serum monoclonal protein (IgG or IgA) level of ≥3 g/dL in the blood and/or clonal bone marrow plasma cells ≥10%; and (2) the absence of end-organ damage (eg, hypercalcemia, renal insufficiency, anemia, bone lesions) that can be attributed to the plasma cell proliferative disorder.

The risk of progression from SMM to symptomatic disease varies over time. In the largest study ever conducted in SMM, investigators at the Mayo Clinic reviewed the medical records of 276 patients who fulfilled IMWG criteria for SMM between 1970 and 1995. Of these, 163 patients (59%) progressed to symptomatic multiple myeloma (MM) or amyloidosis. The overall risk of progression per year was 10% in the first 5 years, 3% in the next 5 years, and 1% in the last 10 years.

Two different models were recently used in small retrospective studies to stratify SMM risk. In one study (N=273), investigators used the Mayo Clinic model, which included three risk factors: clonal bone marrow plasma cells >10%; M-protein >3 g/dL; and free light-chain ratio <0.125 or >8. Progression at 5 years in patients with 1, 2, and 3 risk factors was 25%, 51%, and 76%, respectively. In another study (N=89), investigators used the Spanish PETHEMA model, which included two risk factors: ≥95% abnormal plasma cells and immunoparesis. Progression at 5 years in patients with 0, 1, and 2 risk factors was 4%, 46%, and 72%, respectively. Of interest, a subsequent prospective study (N=77) defined the degree of overlap between the Mayo Clinic and Spanish PETHEMA risk models. In the Mayo Clinic model, 38, 35, and 4 patients were classified as low, medium, and high risk, respectively, compared with 17, 22, and 38 patients, respectively, in the Spanish PETHEMA model. Only four patients were considered to be high risk in both models, and the overall agreement between the two models was only 28.6%.

In addition to the risk factors included in the Mayo Clinic and Spanish PETHEMA models, recent data suggest that certain fluorescence in situ hybridization signatures (t[4;14], t[14;16], and 17p deletions), hyperdiploidy, and the presence of two or more focal processes in the bone marrow, as detected by magnetic resonance imaging, may also be associated with high-risk SMM.

IMWG recommends that patients with SMM be considered for clinical trials to delay and/or prevent progression to symptomatic MM; however, outside of such participation, observation remains the standard of care. The goals of early treatment for SMM should include eradication of disease (cure) and long-term control; all treatment must be viewed within the context of toxicity. In the past 25 years, studies in patients with monoclonal gammopathy of undetermined significance, SMM, and asymptomatic/indolent MM have investigated several therapies, including vincristine/doxorubicin/dexamethasone, melphalan/prednisone, zoledronate, and thalidomide/pamidronate.

Results of the first randomized study in SMM based on novel therapy were published in 2013. In the study, which included 119 patients with SMM who were randomized to treatment (induction with lenalidomide plus dexamethasone followed by maintenance with lenalidomide) versus observation, early treatment was shown to delay disease progression and increase survival. The primary endpoint was time to progression to symptomatic MM; secondary endpoints included response rates, duration of response, progression-free survival (PFS) and overall survival (OS), and safety/tolerability. The criteria for defining high-risk SMM were a hybrid of the Mayo Clinic and Spanish PETHEMA models. Complete response (CR) in the induction and maintenance phases was 14% and 26%, respectively. At median follow-up of 40 months, median time to progression had not yet been reached in the treatment group, but was 21 months in the observation group (hazard ratio for progression, 0.18; 95% confidence interval [CI], 0.09-0.32; P <.001), and 3-year survival was 94% versus 80%, respectively (hazard ratio for death, 0.31; 95% CI, 0.10-0.91; P =.03). Most hematologic and nonhematologic adverse events (AEs) were grade 2 or less, and no patient experienced grade 3 deep vein thrombosis.

A phase II pilot study investigating the addition of carfilzomib to lenalidomide/dexamethasone in 12 patients with SMM is currently ongoing. The primary endpoint is response rate; secondary endpoints include correlative science parameters, duration of response, PFS and OS, and toxicity. After 4 cycles, all 12 patients (100%) had achieved a very good partial response (VGPR) or better, and 7 of 12 patients (58%) had achieved a near complete response (nCR)/CR/stringent complete response (sCR). At a median of 6 cycles, all 12 patients (100%) had achieved nCR/CR/sCR. Furthermore, 11 of the 12 patients (92%) achieving nCR/CR/sCR were negative for minimal residual disease (ie, <20 abnormal plasma cells detected), as assessed by flow cytometry of bone marrow aspirate. The most common nonhematologic grade 3/4 AEs were electrolyte disturbances (n=3; 25%), rash/pruritus (n=3; 25%), elevated liver function (n=2; 17%), and acute kidney injury (n=2; 17%).

Looking to the future, the pathogenesis and biology of SMM must be more clearly elucidated to develop improved biomarkers and optimal early intervention strategies, and also to predict an individual patient’s risk of progression to symptomatic disease.


Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.


This activity is not approved for AMA PRA Category 1 Credit™.

This activity is supported by educational grants from AbbVie, Genentech, Millennium: The Takeda Oncology Company, Novartis Pharmaceuticals Corporation, and Onyx Pharmaceuticals.







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