scholarly journals Safety and efficacy of subcutaneous formulation of bortezomib versus the conventional intravenous formulation in multiple myeloma

2011 ◽  
Vol 3 (2) ◽  
pp. 117-124 ◽  
Author(s):  
Marìa-Victoria Mateos ◽  
Jesús F. San Miguel
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Proteasome Inhibitors ◽  
Subcutaneous Administration ◽  
Standard Of Care ◽  
Intravenous Route ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Dexamethasone ◽  
New Guidelines

The discovery of the ubiquitin–proteasome pathway first, and the proteasome inhibitors thereafter were not made in the hope of improving the treatment of malignant diseases. However, bortezomib, the first in class proteasome inhibitor introduced in the clinical practice has contributed to improve the outcome of patients with multiple myeloma, at relapse or disease progression as well as upfront. The results observed in a large randomized trial (APEX) comparing bortezomib and high-dose dexamethasone demonstrated a significant benefit for bortezomib in terms of response rate, progression-free and overall survival. These results led to bortezomib being approved for use in relapsed and/or refractory myeloma patients. Subsequent studies demonstrated that its activity could be enhanced in combination with other drugs; and the next step was to move to the newly diagnosed patient population; in fact, bortezomib–melphalan–prednisone (VMP) is approved as a standard of care for newly diagnosed elderly patients. However, toxicity, especially peripheral neuropathy, as well as the intravenous route required for its administration are the two most significant bortezomib-related issues. To try to reduce the peripheral neuropathy, new guidelines for its management and the introduction of weekly schedules of administration have contributed to significantly decrease its incidence and the subcutaneous administration has been recently introduce to avoid the intravenous (IV) route. Results obtained in phase I/II and III studies have confirmed that subcutaneous administration is feasible and represents an additional step towards the optimization of bortezomib use, resulting in a probably more convenient method than the IV route that is at least as effective.

How I Treat Frontline Transplant-eligible Multiple Myeloma

Blood ◽  
2021 ◽  
Author(s):  
Aurore Perrot
Keyword(s):  
Multiple Myeloma ◽  
Randomized Clinical Trials ◽  
Human Monoclonal Antibody ◽  
Autologous Transplantation ◽  
Proteasome Inhibitors ◽  
Standard Of Care ◽  
Adaptive Strategy ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Melphalan

High dose Melphalan supported by autologous transplantation is the standard of care for eligible patients with newly diagnosed multiple myeloma for more than 25 years. Several randomized clinical trials have recently reaffirmed the strong position of transplant in the era of proteasome inhibitors and immunomodulatory drugs combinations, demonstrating a significant reduction of progression or death in comparison with strategies without transplant. Immunotherapy is currently changing the paradigm of multiple myeloma management and daratumumab is the first-in-class human monoclonal antibody targeting CD38 approved in the setting of newly diagnosed multiple myeloma. Quadruplets become the new standard in the transplantation programs, but outcomes remain heterogeneous with various response depth and duration. Otherwise, the development of sensitive and specific tools for disease prognostication allows to consider adaptive strategy to a dynamic risk. I discuss in this review the different available options for the treatment of transplant-eligible multiple myeloma patients in frontline setting.

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.

scholarly journals Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasone-containing regimens and the impact of novel agents

Haematologica ◽  
2007 ◽  
Vol 92 (4) ◽  
pp. 546-549 ◽  
Author(s):  
E. Kastritis ◽  
A. Anagnostopoulos ◽  
M. Roussou ◽  
D. Gika ◽  
C. Matsouka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Novel Agents ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Dexamethasone ◽  
The Impact

Carfilzomib PLUS Melphalan and Prednisone (CMP) Is A Promising Combination Therapy For The Treatment Of Elderly Patients With NEWLY Diagnosed Multiple Myeloma: Results Of A PHASE I/II Trial In 68 CASES

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1933-1933 ◽  
Author(s):  
Philippe Moreau ◽  
Brigitte Kolb ◽  
Cyrille Hulin ◽  
Denis Caillot ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Phase I ◽  
Standard Of Care ◽  
Maximum Tolerated Dose ◽  
High Dose ◽  
Newly Diagnosed ◽  
Safety And Efficacy ◽  
Frontline Treatment ◽  
Grade 3

Abstract Melphalan-Prednisone + bortezomib (MPV) is one of the standard of care for the frontline treatment of patients with symptomatic multiple myeloma non eligible for high-dose therapy. In the pivotal VISTA trial for approval of MPV, the main toxicity was grade 3-4 peripheral neuropathy (PN) described in 14% of the cases. Carfilzomib (CFZ), the second-in-class proteasome inhibitor has shown promising activity and a favorable toxicity profile with low PN rates. Therefore, the option of combining CFZ with MP (CMP) is an attractive one. Therefore we designed a phase I/II study to determine the maximum tolerated dose (MTD) of CMP and to assess safety and efficacy. In the phase I portion of the trial, CFZ was started at 20mg/m2, then escalated to 27, 36, and 45mg/m2, administered IV over 30 minutes in 42-day cycles on D1/2/8/9/22/23/29/30 for 9 cycles. Melphalan 9mg/m2 and prednisone 60mg/m2 were given PO D1–4 of every 42-day cycle. MTD was based on dose-limiting toxicity (DLT) in cycle 1 defined as any grade 4 (G4) hematologic adverse event (AE), any hematologic AE preventing aministration of ≥ 2 CFZ doses except G4 thrombocytopenia without bleeding or G4 neutropenia ≤ 7days, ≥ G3 febrile neutropenia, or any ≥G3 nonhematologic AE. As of July 6, 2013, 24 pts have been enrolled in phase I: 6 for each dose level. There were 2 DLTs at 45mg/m2 (fever plus hypotension) resulting in a MTD of 36mg/m2. In Phase II, 44 additional patients received CMP at 36mg/m2 CFZ for N=68 total PhI/II patients (50 patients overall treated at the dose pf 36mg/m2). The median age of the series was 72 years, with 36% of the patients presenting with ISS3. Overall response rate was 89.5% including 56% ≥ very good partial response. With a median follow-up of 12 months, the projected 2y OS was 87%, and the median event-free survival was 22 months. CMP was well tolerated and only 1 patient developed grade 3 PN. These promising results compare favorably to those of MPV, MP+Thalidomide, MP+lenalidomide (R), and R+dex in similar pts. CFZ 36mg/m2 + MP is tolerable and effective in elderly patients with symptomatic newly diagnosed MM. Treatment is ongoing, 20% of the patients are receiving their last cycles of CMP. Final safety and efficacy data will be presented during the meeting. Disclosures: Moreau: CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau. Off Label Use: FRONTLINE TREATMENT WITH CARFIZOMIB. Hulin:CELGENE: Honoraria; JANSSEN: Honoraria. Leleu:CELGENE: Honoraria; JANSSEN: Honoraria. Roussel:CELGENE: Honoraria; JANSSEN: Honoraria. Attal:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau. Facon:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau.

Fatal amebic colitis after high-dose dexamethasone therapy for newly diagnosed multiple myeloma

2010 ◽  
Vol 90 (2) ◽  
pp. 225-226 ◽  
Author(s):  
Chiharu I. Kobayashi ◽  
Go Yamamoto ◽  
Akimasa Hayashi ◽  
Satoshi Ota ◽  
Yoichi Imai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Dose ◽  
Newly Diagnosed ◽  
Amebic Colitis ◽  
High Dose Dexamethasone ◽  
Dexamethasone Therapy

Impact of High Dose Cyclophosphamide on the Outcome of Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4127-4127 ◽  
Author(s):  
Wendi A. Bacon ◽  
Gwynn D. Long ◽  
David A. Rizzieri ◽  
Mitchell E. Horwitz ◽  
John P. Chute ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Retrospective Analysis ◽  
Stem Cell Transplant ◽  
Standard Of Care ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Cell Mobilization

Abstract Abstract 4127 In the age of novel targeted agents, autologous stem cell transplant (ASCT) remains the standard of care for younger patients with newly diagnosed multiple myeloma (MM), offering similar treatment responses and overall survivals as standard chemotherapeutic agents but with the added benefit of a prolonged treatment-free period. Nevertheless, a standard of care for stem cell mobilization for ASCT has yet to be determined. Even in the era of new mobilization agents such as Plerixafor, Cyclophosphamide (Cy) and G-CSF combination remains the preferred mobilizing approach for patients with MM. Several studies have shown that Cy improves the stem cell yield at the expense of increased toxicity, but whether the administration of this chemotherapeutic agent pre-transplant has any impact on the long-term event-free and/or overall survival of myeloma patients remains controversial. In this study, we present a retrospective analysis of 186 patients with newly diagnosed MM who underwent ASCT with high-dose melphalan 200 mg/m2 (HDM) between December of 2000 and 2008 at our Institution. Eighty-three patients were mobilized with single agent G-CSF and 103 patients received high dose Cy (4 gm/m2) and G-CSF combination. Patient characteristics were similar between the treatment groups, including: age, gender, disease stage, and disease status prior to transplant. However, toxicity post-mobilization with Cy/G-CSF was significantly higher compared with G-SCF alone, including: febrile neutropenia (23%), hemorrhagic cystitis (8%), GI toxicity (57%), re-hospitalization due to complications and transplant delay (14%). The overall post-transplant toxicity was similar in the 2 groups, though the treatment related mortality was slightly higher in the Cy/G-CSF arm (4% versus 2%). Post transplant responses were not significantly different in the 2 groups, with 60% of patients achieving a VGPR or better after ASCT in the G-CSF group and 49% in the Cy/G-CSF group (p = 0.33). The median event-free survivals (EFS) for the Cy/G-CSF and G-CSF cohorts were 21.6 and 22.6 months, respectively, (p = 0.62) yielding no significant difference (Figure 1). Similarly, with a median follow up for surviving patients of 34.3 and 32.7 months, the median overall survivals were 68.2 and 62.3 months (p = 0.23) for the Cy/G-CSF and G-CSF cohorts, respectively (Figure 2). This retrospective analysis confirms that the addition of high dose Cy as part of the mobilizing regimen offers no improvement on the transplant outcome for patients with newly diagnosed myeloma and should therefore only be used in cases of difficult stem cell mobilization. Disclosures: No relevant conflicts of interest to declare.

scholarly journals "ROLE OF ALLOGENEIC TRANSPLANTATION IN MULTIPLE MYELOMA IN THE ERA OF NEW DRUGS"

2010 ◽  
Vol 2 (2) ◽  
pp. e2010013 ◽  
Author(s):  
Benedetto Bruno ◽  
Luisa Giaccone ◽  
Moreno Festuccia ◽  
Mario Boccadoro
Keyword(s):  
Multiple Myeloma ◽  
Standard Of Care ◽  
Allogeneic Transplantation ◽  
New Drugs ◽  
High Dose ◽  
Newly Diagnosed ◽  
Stem Cell Rescue ◽  
High Dose Melphalan ◽  
Anti Tumor Activity

High-dose melphalan with autologous stem cell rescue has been regarded as the standard of care for patients with newly diagnosed myeloma up to the age of 65-70 years. The recent development of agents with potent anti-tumor activity such as thalidomide, lenalidomide and bortezomib has further improved overall survival and response rates. However, relapse is a continuous risk.            Allografting is a potentially curative treatment for a subset of multiple myeloma patients for its well documented graft-vs-myeloma effects. However, its role has been hotly debated. Even though molecular remissions have been reported up to 50% after high-dose myeloablative conditionings, their applications, given the high toxicity, have been for long limited to younger relapsed/refractory patients. These limitations have greatly been reduced through the introduction of non-myeloablative/reduced-intensity conditionings.             The introduction of new drugs, characterised by low risks of early mortality, indeed requires to define role and timing of an allograft to capture the subset of patients who may most benefit from graft-vs-myeloma effects.   Ultimately, new drugs should not be viewed as mutually exclusive with an allograft. They may be employed to achieve profound cytoreduction before and enhance graft-versus-myeloma effects as consolidation/maintenance therapy after an allograft. However, this combination should be explored only in well-designed clinical trials.

Sign in / Sign up

Export Citation Format

Share Document