scholarly journals How I treat the young patient with multiple myeloma

Blood ◽  
2018 ◽  
Vol 132 (11) ◽  
pp. 1114-1124 ◽  
Author(s):  
Sara Gandolfi ◽  
Claudia Paba Prada ◽  
Paul G. Richardson
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Proteasome Inhibitors ◽  
High Sensitivity ◽  
Standard Of Care ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Current Standard ◽  
Disease Biology

Abstract The treatment landscape for multiple myeloma has been transformed by the introduction of novel agents, including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. These have been shown to be more effective and generally better tolerated than conventional chemotherapy, with their introduction into clinical practice leading to improved survival. Furthermore, a better understanding of disease biology, improved diagnostic criteria, and the development of sensitive and specific tools for disease prognostication have contributed to better outcome. Treatment in the younger patient can now be individualized based on host and disease features with enhanced monitoring of response and use of high-sensitivity techniques for evaluating residual disease. The current standard of care has been significantly enhanced by novel agents with a paradigm shift toward optional or delayed autologous stem cell transplant as a reasonable choice in selected patients. Conversely, extended treatment with induction of remission followed by maintenance strategies is now a standard of care, conferring prolonged disease control with more manageable toxicities in both the short and long term, as well as improved quality of life.

scholarly journals Update on the role of lenalidomide in patients with multiple myeloma

2018 ◽  
Vol 9 (7) ◽  
pp. 175-190 ◽  
Author(s):  
Sarah A. Holstein ◽  
Vera J. Suman ◽  
Philip L. McCarthy
Keyword(s):  
Multiple Myeloma ◽  
Molecular Mechanisms ◽  
Stem Cell Transplant ◽  
Proteasome Inhibitors ◽  
Standard Of Care ◽  
Myeloma Cell ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Insight Into

Lenalidomide is a derivative of thalidomide and belongs to the class of drugs known as the immunomodulatory drugs (IMiDs). The IMiDs have played a large role in improving the survival outcomes of patients with multiple myeloma. In particular, lenalidomide is currently standard of care in the newly diagnosed setting, in the maintenance setting post-autologous stem cell transplant, as well as in the relapsed/refractory setting. While the combination of lenalidomide and various proteasome inhibitors has proven particularly effective, there are emerging data demonstrating the effectiveness of lenalidomide in combination with other important classes of drugs including the monoclonal antibodies. Recent studies have provided insight into the molecular target of lenalidomide and the other IMiDs, although there is still much to be learned regarding the mechanisms by which lenalidomide affects the myeloma cell and the immune system. Here we review the molecular mechanisms of action, side effects, and the results of the clinical trials which have led to the widespread incorporation of lenalidomide into the myeloma therapeutic armamentarium.

Second Autologous Stem Cell Transplant As Salvage Therapy For Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5529-5529
Author(s):  
Mohamed Elemary ◽  
Mohamed Emara ◽  
Ankur Sharma ◽  
Sabuj Sarker ◽  
Waleed Sabry ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Standard Of Care ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cancer Center ◽  
Cell Transplant ◽  
Time To Relapse

Abstract Introduction Therapeutic options for patients with multiple myeloma whose disease has relapsed after a prior autologous SCT include novel agents, traditional chemotherapy or a second transplant, with no clear standard of care. Limited data are available regarding the value of salvage therapy with a second autologous SCT in patients who relapse after the first one, and the factors that determine the outcome of the second SCT. We retrospectively reviewed our experience at Saskatoon Cancer Center with salvage autologous SCT for relapsed multiple myeloma. Methods Thirty three patients had received a salvage auto-SCT at our institution between February 2000 to February 2012. Median age at second SCT was 60 years (range; 46-71), Median time to relapse after the first SCT was 32 months (range; 3-80). Median interval between the first and second transplant was 34 months (range; 4-85). Re-induction therapy prior to second transplant contained combination with novel therapies (Bortezomib , lenalidomide or Thalidomide) in Thirteen patients ( 40 %) and the rest received conventional combination chemotherapies. Median line of therapies before the second SCT was 1 (range 0-3) with 23 patients (70%) received less than 2 lines and 30% received more than 2 lines. Results Responses to second autologous SCT at day 100 showed CR in 21%, VGPR 30 %, PR 42% with ORR 93 %. Non relapse mortality at day 100 after second transplant was 3 % (no= 1) With a median follow up time of 24 months (range 1-99) from the salvage SCT, the median PFS was 27 months (range 1-89) and the median overall survival (OS) was 36 months ( range 1-99) Eleven patients had TTP inversion (PFS longer after the second transplant) with a median increase of 18 months , of note only two of them received novel agents for salvage, but 70 % required less than two lines prior to salvage SCT. In univariate analysis, patients who had received < 2 lines of therapy prior to salvage SCT (23/33) had significantly higher median TTP of 31 and OS of 52 months, compared to 19 and 33 months for patients who had received ≥2 lines of therapy (10/33). (P = 0.04) Patients who had relapsed more than 2 years post 1st SCT (18/33) had a significantly higher median TTP and OS of 27 and 39 months respectively compared to 22 and 24 months patients who had relapsed less or equal to 2 years (15/33) (P= 0.04) In multivariate analysis, only response to salvage SCT > PR had an impact on TTP and OS; however it was not statistically significant. Conclusion Second salvage auto-SCT generally is safe and effective in patients with relapsed multiple myeloma. Patients with ≥2 prior lines of therapy and a TTP after initial transplant of ≤24 months are unlikely to benefit significantly. Salvage auto-SCT should therefore be considered for appropriate patients with relapsed multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2887
Author(s):  
Timothy J Voorhees ◽  
Anne W Beaven
Keyword(s):  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Standard Of Care ◽  
The United States ◽  
Autologous Stem Cell Transplant ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Novel Agents ◽  
Cell Transplant ◽  
T Cell Therapy

Hodgkin lymphoma (HL) is a B-cell malignancy representing approximately one in ten lymphomas diagnosed in the United States annually. The majority of patients with HL can be cured with chemotherapy; however, 5–10% will have refractory disease to front-line therapy and 10–30% will relapse. For those with relapsed or refractory (r/r) HL, salvage chemotherapy followed by autologous stem cell transplant (ASCT) is standard of care, but half of patients will subsequently have disease progression. Relapse following ASCT has been associated with exceedingly poor prognosis with a median survival of only 26 months. However, in recent years, novel agents including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab) have been shown to extend overall survival in r/r HL. With the success of novel agents in relapsed disease after ASCT, these therapies are beginning to show clinically meaningful response rates prior to ASCT. Finally, a new investigation in r/r HL continues to produce promising treatment options even after ASCT including CD30 directed chimeric antigen receptor T-cell therapy. In this review, we will discuss the recent advances of BV and anti-PD-1 therapy prior to ASCT, novel approaches in r/r HL after ASCT, and review active clinical trials.

Treatment of Relapsed and Refractory Multiple Myeloma in Patients with p53 Deletion.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1724-1724
Author(s):  
Donna E. Reece ◽  
Young Trieu ◽  
Hong Chang ◽  
Wei Xu ◽  
Peter Anglin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Alkylating Agents ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Time Period ◽  
Investigational Drugs ◽  
Beta 2 Microglobulin

Abstract p53 deletion by fluorescence in situ hybridization (FISH) has been reported in about 10% of newly diagnosed patients (pts) with multiple myeloma (MM) and has been associated with a poor prognosis. Previous data from our centre has demonstrated that the progression-free survival (PFS) and overall survival (OS) of these pts after a single autologous stem cell transplant (ASCT) is only 16.9 and 48.2 months, respectively, compared to 24.4 and 76.6 mos, respectively, in all pts transplanted during the same time period (Mikhael et al, Blood2007; 110: abstract 953). Minimal information is available on the treatment (Tx) and course of these pts following disease progression. Therefore, we performed a retrospective review of all MM pts treated at our institution who were found to have p53 deletion. We identified 31 pts with relapsed/refractory (rel/ref) MM with this cytogenetic abnormality. At diagnosis, median age was 54 years (range, 31–70), hemoglobin 97 g/L (range, 67–149), creatinine 96 μmol/L (range, 28–1751), beta 2-microglobulin 314 nmol/L (range, 225–437), CRP 3 mg/L (range, 2–7) and LDH 205 U/L (range, 82–478); 58% were male. Immunoglobulin subtypes included: IgG (14 pts), IgA (8 pts), IgD (2 pts) and light chain only (7 pts). Concomitant cytogenetic abnormalities included 13q deletion in 68% and t(4;14) in 67% of pts evaluable. Thirty-nine percent developed plasma cell leukemia (PCL) at some point in the disease course, which was associated with a poor OS (p=0.005). All but 5 had undergone prior ASCT with a median time from diagnosis to ASCT of 8 (95% CI, 4–145) mos. Txs given for rel/ref MM consisted of the following regimens: thalidomide-based in 15, bortezomib-based in 12, lenalidomide-based in 11, alkylating agents in 9 and steroids only in 5 pts, and other regimens (D-PACE or investigational drugs) in 7 pts. The median follow-up from diagnosis in these pts is 45 (95% CI, 4–145) mos. The overall response rate (≥PR) (ORR), median PFS and median OS from the start of each regimen is shown below. Agent Median duration of Tx (mos) ORR(%) Median PFS (mos) Median OS (mos) Thalidomide 6.2 20% 5.0 11.9 Bortezomib 5.2 50% 5.6 36.1 Lenalidomide 10.6 60% 4.8 36.1 Alkylating agents 6.0 11% 5.1 30.0 Steroids 1.9 20% 1.9 33.4 Other 2.2 43% 6.3 33.4 We conclude: 1) Median PFS in pts with the p53 deletion is less than 6 months, with an OS of 2.5–3 yrs; 2) novel agents other than thalidomide produce the highest ORR in rel/ref MM with p53 deletion; 3) the short OS in the thalidomide group is likely related to the unavailability of other novel agents for subsequent relapses, as the majority of the pts were treated before 2004; 4) better strategies/drugs are required for these pts.

Efficacy of Novel Agents in Multiple Myeloma in Comparison to Autologous Stem Cell Transplant: A Retrospective Study in a Single Inner City Institution

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5118-5118
Author(s):  
Tareq Braik ◽  
Dayra Avila ◽  
Shivi Jain ◽  
Manila Gaddh ◽  
Barabara Yim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Median Survival ◽  
Standard Of Care ◽  
High Dose Chemotherapy ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Conventional Chemotherapy ◽  
Novel Therapy

Abstract Abstract 5118 Introduction: Since the mid 1990s, high dose chemotherapy with hematopoietic stem cell rescue has been considered the standard of care for front-line treatment in younger patients with multiple myeloma. This standard of care has been based on randomized controlled trials that compared autologus stem cell transplant (ASCT) with conventional chemotherapy. During the past decade, novel agents (NA), thalidomide, bortezomib and lenalinomide, have replaced conventional chemotherapy in the treatment of myeloma. These agents, used frontline, have shown promise in improving the outcome of myeloma patients without increasing toxicity. There are no studies to date comparing NA therapy to ASCT to determine whether there is a survival difference or whether NA therapy may reduce the need for transplantation. Many of our patients have no health insurance coverage and transplant is not a therapeutic option for them. We have attempted to compare the outcome of such patients receiving NA therapy with those in the literature who received conventional chemotherapy followed by ASCT. Methods: Ninety nine patients with multiple myeloma were treated at John H Stroger Hospital of Cook County between 2001 and 2011. All patients received novel agents (thalidomide, bortezomib and lenalinomide) as part of their therapy. Only 18/99 (18.2%) went for high-dose chemotherapy with ASCT and the remaining 81/99 (81.8%) received novel therapy without ASCT. We compared the outcome of patients who received novel therapy alone to a historical control group from the literature who received ASCT with conventional therapy (N Engl J Med 2003;348:1875–83). Overall survival was determined by Kaplan-Meier estimates. Results: We evaluated 99 consecutive myeloma patients (38% males and 61% female) of which 65% were African Americans, 19% Hispanics and 7% whites. All 3 stages (international staging system) of myeloma were equally represented. The median age at diagnosis was 60 years (40–85yr). Median follow up was 48 months (12–120). During the ten year follow up period, 60 patients (60.4%) have died. Twenty four out of 99 patients (24.2%) received only one line of therapy. 75 patients received more than one line of therapy. 75% received thalidomide-based therapy, 13% received bortezomib-based therapy and 12% received lenalinomide-based therapy. The median survival of patients who received novel therapy without ASCT (n=81) was 60 months, which is higher than the median survival of the historical controls who received ASCT reported by Child et al, N Engl J Med 2003;348:1875–83, (median survival = 54.1 months), the difference was statistically significant (P=0.0329). There was no statistically significant difference between the two groups by sex (p=0.927) and race (p=0.421). The 5-year survival of patients who received novel therapy without ASCT (n=81) was 48.2%. For those who were younger than 65 years (n=54), the median survival was 72 months and the 5-year survival was 58.1% in comparison to those who were 65 years and older (n=27), the median survival was 46 months and the 5-year survival was 29.2% (P=0.029). Conclusion: Novel agents are effective frontline therapy for multiple myeloma, especially in patients younger than 65. Our cohort had remarkable results in comparison to a historical population of patients who had ASCT with conventional chemotherapy. Since there is no curative therapy to date, a prospective randomized trial comparing NA with ASCT will be essential to clarify the role of ASCT in the era of novel therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Phase II Study of the Combination of Interleukin-2 with Zoledronic Acid As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5697-5697 ◽  
Author(s):  
Gabriele Buda ◽  
Rita Fazzi ◽  
Giovanni Carulli ◽  
Sara Galimberti ◽  
Paola Sammuri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Zoledronic Acid ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Gamma Delta

Abstract Background: Multiple myeloma is still today an incurable disease. The many therapeutic techniques and new therapies proposed in recent years have extended survival but did not allow for healing. Further study allowed to demonstrate that a maintenance could be useful to control the progression of disease. However, there is no clear indication for which maintenance has to be used after a first line of induction therapy. The technique of allograft, used in patients at highest risk, demonstrates that the immune response to the residual disease plays a key role in the success of this technique. Among the major players in response to myeloma, in allogeneic stem cell transplantation, gamma delta lymphocytes play a significant action: complete response after allogeneic few months later (also the molecular level) happen in parallel with the presence in the bone marrow of a significant proportion of lymphocytes with gamma delta oligoclonal expression of TCR rearrangements. Zoledronic acid induces proliferation of these cells by the production of several cytokines, in particular interleukin-2 (IL-2). Furthermore, T lymphocytes Vdelta2 are proved to be crucial antineoplastic mediators and, after expansion in vitro, capable of controlling tumor growth in animal models. These data confirm the hypothesis that gammadelta lymphocytes have a role in controlling the growth of myeloma plasma cells and can be active on the residual disease after autologous stem cell transplant. We planned to evaluate the role of the association of Zoledronate and IL-2 in vivo as post ASCT maintenance therapy in patients with newly diagnosed multiple myeloma (NDMM). Methods: This is a single arm phase II multicenter ongoing study of the combination of IL-2 with zoledronic acid as maintenance therapy for NDMM patients post ASCT. The primary objective was to establish safety and efficacy of IL-2 as maintenance therapy. The secondary objective was to evaluate the immunological expansion of gamma delta lymphocytes. Eligible patients had undergone ASCT, with melphalan as a preparative regimen. At July 2016, forty two patients in very good partial remission (VGPR) have been enrolled in the study (total planned enrollment: 43 pts) and started maintenance therapy 90-180 days post ASCT. Maintenance schedule included IL2 and zoledronic acid. IL2 was administered at a fixed dose of 2 x 106UI from day 1 to day 7 for the first cycle and with the maximum tolerated dose (up to a max of 8 x 106UI) from day 1 to day 7 for subsequent cycles (dose escalation of 25% in each cycle in the absence of toxicity). Zoledronic acid was infused 4 mg iv on day 2. This dosing regimen is repeated every 28 days until disease progression. Adverse events were graded by NCI-CTCAE v4. Response was assessed by the modified International Uniform Response Criteria. Results and toxicity: 42 patients (pts) have been enrolled with a median age of 59 (range 42-72); 50% were male and 50% female. All the 42 pts have received a median of 11 cycles (range 1-23). Of the 42 pts 21 remain on therapy (data at July 2016), 21 pts are off study: 9 due to progressive disease (PD) and 12 due to consent withdrawal. Among the 9 pts with PD, the median PFS post ASCT was 12 months (2-18 months). Of the 42 pts, 33 (79%) not progressed after a median of 13 months (range 1-33) and the median PFS has not been reached. 7/42 patients (17%) reached complete remission. Peripheral and bone marrow analysis of gamma delta lymphocytes expansion to evaluate the level of immune response is still under examination. Grade 1/2 hematologic adverse events (AEs) included: grade 1 (G1) anemia (3 pts), G1 neutropenia (3). Grade 1/2 drug-related non-hematologic AEs included: G1 fever (25) G2 fever (8); G2 constitutional symptoms (joint pains) (20); G2 constipation (4); G1/2 nausea (10); G1 fatigue (15), G1/2 cutaneous rash (2). Conclusions: Long term administration of combination of IL-2/zoledronate as maintenance therapy post ASCT is feasible. The incidence of non hematologic adverse events (in particular fever) were manageable with no dose escalation of IL-2 over 5 x 106UI. This immunological approach, without any chemotherapeutic drug, seems to be able to control the disease and to obtain the complete remission in a subgroup of myeloma patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals VD Versus VTD Induction: Similar Efficacy in Controlling Disease in Transplant Eligible Multiple Myeloma Patients Outside Clinical Trials

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5711-5711
Author(s):  
Federica Cocito ◽  
Silvia Mangiacavalli ◽  
Virginia Valeria Ferretti ◽  
Claudio Salvatore Cartia ◽  
Maya Ganzetti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Control ◽  
Real Life ◽  
Standard Of Care ◽  
Similar Efficacy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Overall Response ◽  
Free Rate

Abstract Autologous stem cell transplant (ASCT) remains the standard of care for Multiple Myeloma (MM) patients younger than 70 years old. The role of induction therapy is crucial within a program of high-dose therapy since deeper is the response before, higher is the outcome of transplant. In this study, we analyzed a real life setting of patients treated with three different induction approaches: VAD (Vincristine-Adriamycin-Dexamethasone), VD (Bortezomib - Dexamethasone), and VTD (Bortezomib-Thalidomide-Dexamethasone) in terms of depth of response, 2 years therapy-free rate and toxicity. One hundred and sixty-three MM patients (pts) were included in the analysis: 62 pts treated with VAD (38%), 44 with VD (27%) and 57 with VTD (35%). In VTD group 49 pts (86%) received Bortezomib subcutaneously. As shown in Table 1, patients of the three groups were similar for D&S stage (p 0.59), a higher rate of ISS stage 3 was observed in VAD group (p=0.019), patients in VTD group were significantly older (p=0.024), median follow-up was significantly lower in VTD pts (p<0.001). The overall response rates after induction were similar in all three groups (p=0.156), with higher rate of responses of good quality (CR+VGPR) for patients treated with Bortezomib-based combinations: VAD 24.2%, VD 52.3%, VTD 63.2% (p<0.001). No difference was observed between VTD and VD (p=0.258). A different pattern of responses was observed after transplant, VTD, in fact, was superior to VAD (p<0.001) and VD (p=0.012), while no difference was highlighted between VAD and VD (p=0.352). As a matter of fact, 2 years therapy-free rate were: 48% for patients treated with VAD vs 73% with VD vs 74% with VTD (p=0.189). Of note, however, bortezomib base therapy maintained its superiority with respect to VAD (p=0.03). No differences were observed between VD and VTD regimens in terms of toxicity of any grade and type (52.3% VD vs 52.6% VTD, p> 0.9), and of discontinuation rate (14% in VTD and 18% in VD, p=0.395). The incidence of all grades peripheral neuropathy (PN) was similar between VD and VTD (28.2% and 31.4% p=0.835), but grade 3-4 PN was significantly higher in VD group (no patients in VTD vs 18% in VD pts, p=0.078), probably due to different way of Bortezomib administration in VTD group (86% of pts received subcutaneous Bortezomib). In this study, we confirm that Bortezomib-based regimens are better than VAD in terms of overall response rate, good quality responses and long-term disease control. VTD is superior to VD in terms of good quality responses after transplant but disease control at 2 years is similar. Disclosures Corso: Janssen-Cilag: Honoraria.

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