Uninvolved immunoglobulins predicting hematological response in newly diagnosed AL amyloidosis

2016 ◽  
Vol 41 ◽  
pp. 56-61 ◽  
Author(s):  
Eli Muchtar ◽  
Hila Magen ◽  
Gilad Itchaki ◽  
Amos Cohen ◽  
Ra’ama Rosenfeld ◽  
...  
Keyword(s):  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Hematological Response

scholarly journals Upfront Ixazomib Plus Dexamethasone Induce Promptly Hematological Response in Patients with Light-Chain Amyloidosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1908-1908 ◽  
Author(s):  
Zheng Wei ◽  
Yian Zhang ◽  
Jing Li ◽  
Peng Liu
Keyword(s):  
Light Chain ◽  
Proteasome Inhibitor ◽  
Response Rate ◽  
Stage Iii ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Light Chain Amyloidosis ◽  
Hematological Response ◽  
Hematological Remission ◽  
Grade Iii

Background: CyBorD (bortezomib, cyclophosphamide, and dexamethasone) is considered as an effective induction regimen in newly diagnosed light chain amyloidosis (AL) patients. Although a full dose of dexamethasone (Dex) leads to a higher response rate, the dose is strictly limited, usually because of fluid retention. Additionally, supervised administration of bortezomib weekly, if applied, increases the cost and inconvenience of treatment for service providers and patients.Ixazomib(IXA), an oral proteasome inhibitor, was reported highly effective as a single agent in relapsed or refractory AL amyloidosis. The objective of this observation is to evaluate the feasibility and efficiency of adding a lower dose of Dex to IXA (Id) as an upfront regimen in AL pts. Patients and Methods: Between 9/29/2018-4/1/2019, twenty-five newly diagnosed (ND) AL pts were sequentially enrolled. All AL pts had positive Congo Red staining in biopsy specimens confirmed by immunoelectron microscopy(IEM). Ixazomib 4mg D1,8,15 and Dexamethasone 10mg D1,8,15,22 were given for a 28-day schedule until disease progression or intolerance. Efficiency and safety profiles were assessed at the beginning of each cycle. Patients who had not achieved PR after 3 cycles received additional oral cyclophosphamide (50mg daily). The patients not achieving PR after 3 more cycles would switch to salvage therapies such as lenalidomide-base regimens or melphalan-based regimens. Upfront Id regimen can be prolonged for 2 cycles after a best hematological response (CR) has been achieved. The primary objective was to determine the response rate of this regimen and to evaluate the safety and tolerability of Upfront Id. Secondary objectives included PFS and OS. Results: Patients(n=25) received a median of 4 cycles (1-8) of Id regimen. Most patients were at late stage (20 pts in MAYO stage III, 4 pts in stage I and 1 pts in stage II). The interphase FISH analysis in BM plasma cells finds translocation t(11,14) in 8 pts.(Table 1) All patients were evaluable for toxicity and twenty-four for the response. The ORR was 66.7%(16/24) post cycle 1 and 70.8%(17/24) post cycle 4. Best hematological response achieved to date of this study is CR in 10pts, VGPR in 5 pts. 5 of the 7 pts did not reach their hematological remission have a t(11,14) translocation. With a median of 197 days (34-281) follow-up, 68%(17/25) of the patients were still alive, and 41.7%(10/24) with their best hematological response. 4 of the patients died of sudden and the rest due to the progression of heart failure. (Figure 1) According to CTC AE 5.0, Grade III/IV AEs (no. of pts) included: diarrhea 16%(4), thrombocytopenia 12%(3), general edema 8%(2), hypokalemia 8%(2), AST increased 4%(1), hyperuricemia 4%(1), and pneumonitis 4%(1). All the 4 patients with serious diarrhea quit therapy because of intolerance. (Table 2) Conclusions: Adding low dose dexamethasone to Ixazomib can induce rapid and profound hematological remission in newly diagnosed AL pts, especially in patients without t(11,14). This entirely oral, chemotherapy-free combination regimen ensures patients' compliance. The relatively low incidence of Grade III/IV AEs also makes the regimen seemingly a broad usage in MAYO stage III pts. However, diarrhea and thrombocytopenia in these patients still need awareness. OffLabel Disclosure: Ixazomib (Ixa) is the first oral proteasome inhibitor that approved for the use in patients with relapsed/refractory multiple myeloma (RRMM) in > 60 countries including US and China. In this single-center real-world study, we present the efficacy and safety profile of Ixazomib-based therapy as frontline therapy in patients with AL amyloidosis.

Uninvolved Immunoglobulins Predicting Hematological Response in Newly Diagnosed AL Amyloidosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4262-4262
Author(s):  
Eli Muchtar ◽  
Hila Magen ◽  
Gilad Itchaki ◽  
Amos Cohen ◽  
Raama Rosenfeld ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Relative Difference ◽  
Al Amyloidosis ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
Reference Levels ◽  
First Line ◽  
Hematological Response ◽  
First Line Treatment

Abstract Introduction: Immunoparesis serves as a marker for progression in plasma cell proliferative disorders. However, the impact of immunoparesis in AL amyloidosis has not been addressed yet. Additionally, immunoparesis can vary from mild suppression to a major decrease in the uninvolved Immunoglobulins, but this has not been carefully studied. Methods: Immunoparesis was defined qualitatively as any decrease below the low reference levels of the uninvolved immunoglobulins and quantitatively, as the relative difference between the uninvolved immunoglobulins and the lower reference levels' values. Results: Forty-one newly diagnosed AL amyloidosis patients were included. The median age was 67.2 years (range, 46-87). At the time of treatment initiation, 14 patients (34%) had preservation of the uninvolved Ig's while 27 patients (66%) had suppression of the uninvolved Ig's. Patients with any degree of immunoparesis had higher percentage of marrow plasma cells compared to patients with preserved levels of the uninvolved Ig's (median 25% vs. 15%, P=0.02). Regarding quantitative assessment of immunoparesis, the median relative difference of the uninvolved immunoglobulins was 18% above the lower reference levels [range (-71%)-210%]. Ninety percent of patients were treated with novel agents-based regimens, mostly bortezomib-containing regimens. Nineteen percent of patients did not attain response to first line treatment. There was no difference in the overall response rate between patients with preserved levels of the uninvolved Ig's compared to patients with immunoparesis [odds ratio (OR) for partial response and better vs. no response - 4.55 (95% CI 0.5-41.4), P=0.22]. However, patients with a relative difference of the uninvolved Ig's below -25% from the lower reference levels were less likely to respond to first line treatment compared to patients with a relative difference of -25% and above [OR for no response vs. PR and better 30 (95% CI 4.1-222.2), P=0.0004]. Patients who failed first line treatment were successfully salvaged with lenalidomide-based treatment. Median follow-up was 13 months (range, 1-86). Median Progression-free survival (PFS) and overall survival were 14 and 42.5 months, respectively. PFS differed between those with a relative difference of the uninvolved Ig's below -25% compared to those with a relative difference of -25% and above (6.7 vs. 26.8 months), without statistical significance (P=0.17). There was no significant difference in overall survival between the sub-groups. Conclusions: This study suggests a correlation between the depth of immunoparesis and hematological response to bortezomib-containing regimens in newly diagnosed AL amyloidosis patients. Furthermore, its results imply a favorable response to lenalidomide in AL amyloidosis patients with significant immunoparesis. Disclosures Raanani: Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Ariad: Consultancy, Research Funding; BMS: Consultancy.

scholarly journals Rapid and Deep Hematologic Responses Are Associated with Improved Major Organ Deterioration Progression-Free Survival in Newly Diagnosed AL Amyloidosis: Results from Andromeda

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Ashutosh D. Wechalekar ◽  
Giovanni Palladini ◽  
Giampaolo Merlini ◽  
Raymond L. Comenzo ◽  
Arnaud Jaccard ◽  
...  
Keyword(s):  
Research Funding ◽  
Progression Free Survival ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Free Survival ◽  
Major Organ ◽  
End Stage

Background: As immunoglobulin light chains present in AL amyloidosis are considered to be toxic to involved organs, especially the heart, rapid and deep hematologic remission with reduction of these light chains with frontline therapy may be crucial to improving long-term clinical outcomes. ANDROMEDA (NCT03201965) is the first phase 3 study in this patient population to evaluate major organ deterioration progression-free survival (MOD-PFS), a composite endpoint of time to end-stage cardiac disease (requiring cardiac transplant, left ventricular assist device, or intra-aortic balloon pump); end-stage renal disease (requiring hemodialysis or renal transplant); hematologic progression per consensus guidelines1; and death. Here, we report the impact of early and deep hematologic responses on MOD-PFS. Methods: ANDROMEDA is a randomized, open-label, active-controlled phase 3 study of patients with newly diagnosed AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (VCd) ± daratumumab subcutaneous (DARA SC; DARA 1800 mg coformulated with recombinant human hyaluronidase PH20 in 15 mL). Key eligibility criteria were newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage I-IIIA, eGFR ≥20 mL/min, and absence of symptomatic multiple myeloma. Disease evaluations occurred every 4 weeks during Cycles 1-6. Hematologic responses were adjudicated by an Independent Review Committee. Landmark analyses for response were performed at 1 and 3 months (± 7 days). Analyses of hematologic responses and MOD-PFS were performed on the intent-to-treat analysis set. Patients without a baseline or post-baseline assessment were censored at randomization for the MOD-PFS analysis. Hazard ratios and corresponding 95% confidence intervals were estimated based on Cox proportional hazard model. Results: A total of 388 patients were randomized to DARA-VCd (n=195) or VCd alone (n=193). Baseline characteristics were well balanced between groups. The proportions of patients with heart and kidney involvement were 71% and 59%, respectively. Median follow-up was 11.4 months (range, 0.03-21.3+). For the 1- and 3-month landmark analysis, hematologic response was available for 356 and 289 patients, respectively. Hematologic response rates by treatment group at 1 and 3 months are shown in the Table. MOD-PFS was longer in patients with complete response (CR)/very good partial response (VGPR) at 1 and 3 months vs patients with lower levels of response (Figure). CR/VGPR at 1 and 3 months was associated with reduced risk of death or major organ deterioration in a multivariate analysis adjusting for baseline difference between involved and uninvolved free light chains and cardiac stage, (HR: 0.399, P=0.0006 and HR: 0.262, P=0.0003, respectively). At 1 and 3 months, cardiac and renal response rates were higher in those who achieved early and deep hematologic responses (CR and VGPR). Conclusions: CR/VGPR at 1 and 3 months was associated with a reduced risk of major organ deterioration and death in patients with newly diagnosed AL amyloidosis. These data confirm that initial therapy that achieves rapid and deep hematological responses is essential to improving long-term outcomes in AL amyloidosis. Reference 1. Comenzo RL, et al. Leukemia. 2012;26(11):2317-25 Disclosures Wechalekar: Janssen: Honoraria, Other: Advisory; Caelum: Other: Advisory; Celgene: Honoraria; Takeda: Honoraria, Other: Travel. Palladini:Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other. Comenzo:Caleum: Consultancy; Unum: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Jaccard:Celgene: Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Celgene., Research Funding; Janssen: Consultancy, Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Janssen., Research Funding. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Pei:Janssen: Current Employment, Current equity holder in publicly-traded company. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Kastritis:Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding.

scholarly journals Efficacy of Modified Vrd-Lite for Transplant Ineligible Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-4
Author(s):  
Mizuki Ogura ◽  
Tadao Ishida ◽  
Moe Nomura ◽  
Hirofumi Irita ◽  
Junichiro Nashimoto ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Multiple Myeloma ◽  
Cardiac Amyloidosis ◽  
Staging System ◽  
Treatment Interruption ◽  
Cardiac Complications ◽  
High Dose ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
The Impact

BACKGROUND: High dose chemotherapy followed by autologous peripheral blood stem cell transplantation is an effective treatment for multiple myeloma. However, many patients with newly diagnosed multiple myeloma are transplant-ineligible because of their age and complications, result in a poorer prognosis than transplant-eligible patients. Furthermore, many of them cannot complete normal chemotherapy because of low tolerability. Here, we investigated the efficacy and safety of modified bortezomib with lenalidomide and dexamethasone (mVRD-lite) for transplant-ineligible patients with newly diagnosed multiple myeloma. STUDY DESIGN: A retrospective observational analysis was performed on patients who received mVRd-lite for the first line chemotherapy between Jan. 2016 and Mar. 2020 in our hospital. Patients who received high dose dexamethasone to reduce tumor burden, and patients who received bortezomib with dexamethasone or lenalidomide with dexamethasone as a reduction regimen of mVRd-lite were also included. We evaluated ORR, OS, PFS and adverse effect. mVRD-lite at first was administered over a 28-day cycle. Bortezomib 1.3 mg/m2 weekly was administered subcutaneously on days 1, 8, 15 and 22. Lenalidomide 15 mg was given orally 18 days, omitted on days 1, 8, 15, which are the days of bortezomib administration. Dexamethasone 20 mg was given orally on days 1, 2, 8, 9, 15, 16, 22, which are the day of and day after bortezomib. We also reviewed patients background, especially complication of light-chain amyloidosis and considered the impact of cardiac amyloidosis on patient prognosis. This study was conducted with the permission of the Ethics Review Board in our hospital. RESULTS: The subjects analyzed totaled 40 transplant-ineligible patients. 11(27.5%) patients were AL amyloidosis associated with multiple myeloma and 8(20%) patients had cardiac amyloidosis. Median age at diagnosis was 73 (range 48-86) and Male:Female=1:1. Most of them were judged inadequate to transplantation due to their age, general condition, or complication. One patient was ruled unfit to transplantation, because of his refusion. The Revised International Staging System (R-ISS) were I in 5 (12.5%), II in 25 (62.5%) and III in 8 (20%). 5(25%) patients switched to maintenance therapy. 17(42.5%) patients discontinued treatment, because of adverse effect (cardiac failure 4 ; two of them combined with cardiac amyloidosis, rash 4, peripheral neuropathy 3, infection 3, etc). 2(5%) patients died during treatment by mVRd-lite, because of Grade 4 adverse effect, such as pneumonia. 11(27.5%) patients died during observation period and causes of death were primary disease and TRM. 1(2.5%) patient was died of heart failure associated with cardiac amyloidosis. The overall response rate(ORR) during treatment period of mVRd-lite was obtained in 34(85%), including sCR in 5 (12.5%), VGPR in 13 (32.5%) and PR in 14(30%). 2(5%) patients achieved MRD negative. SD were observed in 3(7.5%) patients. 3(7.5%) patients were not evaluated efficacy because of treatment interruption by adverse effect. Overall survival rate at two year is 64.3%, median OS was not reached, at a median follow-up of 20 months. CONCLUSIONS: Transplant-ineligible multiple myeloma patients are associated with poor prognosis. Modified RVD-lite is one of the appropriate therapeutic options, in the transplant-ineligible multiple myeloma patients. Twenty-five percent of patients with cardiac amyloidosis had treatment discontinued due to cardiac complications. Further study is needed for treatment of patients with multiple myeloma complicated with cardiac amyloidosis. Disclosures Ishida: Janssen: Speakers Bureau; Celgene: Speakers Bureau; Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau. Nashimoto:Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Suzuki:Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Bristol-Myers Squibb, Celgene and Amgen: Research Funding.

High-Dose Therapy in AL Amyloidosis: A Prospective Phase II Study by the Dutch-Belgian Cooperative Group (HOVON)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 163-163 ◽  
Author(s):  
Bouke P.C. Hazenberg ◽  
Sandra Croockewit ◽  
Ron van der Holt ◽  
Sonja Zweegman ◽  
Gerard Bos ◽  
...  
Keyword(s):  
Clinical Response ◽  
Phase Ii Study ◽  
Cell Clone ◽  
Performance Status ◽  
Complete Response ◽  
High Dose ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Cardiac Ejection Fraction

Abstract Background: AL amyloidosis is generally caused by a kappa or lambda light-chain producing plasma cell clone in the bone marrow. High-dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) is effective in AL amyloidosis. Pretreatment of these patients with vincristine, doxorubicin and dexamethasone (VAD) may have a rapid and additive effect on the underlying plasma cell clone. Objective: To study the feasibility and efficacy of VAD followed by HDM and ASCT in AL amyloidosis. Patients and Methods: In a prospective multicenter phase II study, the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) studied the effect of three courses of VAD followed by HDM with ASCT on hematological and clinical response rates and overall survival in AL amyloidosis. Untreated patients aged ≤ 65 years with proven AL amyloidosis and monoclonal gammopathy or multiple myeloma stage I were included. Patients with recent prior malignancy, other types of amyloidosis, and severe other diseases not related to AL amyloidosis were excluded. High risk was defined as cardiac septum ≥ 15 mm, cardiac ejection fraction ≤ 55%, creatinine > 177 μmol/L, or bilirubin > 34 μmol/L (Dispenzieri et al, J Clin Oncol2001; 19:3350–6). All patients were treated with VAD or dose-modified VAD and after the third course re-evaluated. Patients were judged eligible for stem cell collection and ASCT if WHO performance status 0–2, NYHA class 1–3, cardiac ejection fraction >45%, and no severe other disease. Hematological response was defined as complete response (disappearance of monoclonal protein in blood and urine, and no clonal excess of plasma cells in bone marrow), partial response (greater than 50% reduction in serum and urine monoclonal proteins), persistence, and progression (doubling of monoclonal protein in serum or urine). Clinical response was defined as organ response, stabilization, or progression (Gertz et al, Am J Hematol2005; 79:319–28). Results: Sixty-nine newly diagnosed patients with AL amyloidosis were included between September 2000 and January 2006: 37 men and 32 women with a median age of 55 years and WHO performance status 0–2. Organ involvement was renal in 58 (84%), cardiac in 32 (46%), hepatic in 12 (17%), and neuropathic in 18 (26%); 15 patients (22%) had involvement of 3 or 4 organs. Thirty-seven (54%) could be classified as high-risk patients. Forty-six patients (67%) could proceed to HDM (140–200 mg/m2) after VAD induction. The transplants were performed in tertiary referral centres. Median haematological recovery time of ANC > 1.0 × 109/L and platelets > 50 × 109/L was 17 and 21 days, respectively. End of survey was November 2007. Overall hematological response was 39% including 16% with a complete response. Overall clinical response was 26% and stabilization in 35%. In 43% of patients only the clinical response could be assessed. Overall survival of all patients was median 60 months and had not been reached for the transplanted patients (Figure). Nine patients died from TRM (11%), 7 during VAD and 2 following HDM. Side effects CTC grade ≥ 2 were recorded in 46% of patients during VAD induction and in 87% of patients after HDM; infections CTC grade ≥ 2 were recorded in 13% and 65%, respectively. Conclusions: VAD induction followed by HDM and ASCT for AL amyloidosis is feasible, has acceptable TRM, and results in a remarkable prolonged survival. This two-step approach of induction with non-intensive chemotherapy in all patients followed by HDM with ASCT in eligible patients is now recommended as standard treatment by HOVON for newly diagnosed patients with AL amyloidosis who are eligible for high-dose therapy. Figure Figure

A Multicenter Phase I/II Dose Escalation Study of Lenalidomide in Combination with Melphalan and Dexamethasone in Subjects with Newly-Diagnosed Light-Chain (AL)-Amyloidosis.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1732-1732
Author(s):  
Philippe Moreau ◽  
Arnaud Jaccard ◽  
Lotfi Benboubker ◽  
Bruno Royer ◽  
Valerie Coiteux ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Response Rate ◽  
Standard Dose ◽  
High Dose ◽  
Al Amyloidosis ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Open Label ◽  
Dose Escalation Study

Abstract A recent prospective randomized trial comparing standard-dose to high-dose melphalan in patients presenting with newly diagnosed AL-amyloidosis showed that oral melphalan-dexamethasone (M-dex) given monthly could be considered the current standard of care, with a median survival of 56 months (Jaccard, N Engl J Med 2007). The use of a combination of lenalidomide and dexamethasone has also been tested in patients with symptomatic AL-amyloidosis. The initial dose of lenalidomide at 25 mg/day was poorly tolerated. However, a 15 mg/day dose regimen was well tolerated and effective, with both hematologic and organ responses (Dispenzieri, Blood 2007 & Sanchorawala, Blood 2007). Combining M-dex with lenalidomide (M-dex-rev) could increase the response rate but the toxicity of this regimen is still unknown. Thus we have initiated a multicenter single-arm open-label phase I/II dose escalation study of lenalidomide administered in combination with M-dex. The primary endpoint was the incidence of dose limiting toxicities (DLT) during the first cycle of lenalidomide at a given dose level in order to determine the maximum tolerated dose (MTD). In addition to melphalan 0.18mg/kg/day from day 1–4 of each 28 day cycle and dexamethasone 40mg/day from day 1– 4 of each 28 day cycle, 3 cohorts of 3 subjects were successively exposed to escalating doses of lenalidomide (5, 10 and 15mg once daily on days 1–21 of a 28 day cycle). DLT was defined using National Cancer Institute (NCI) common toxicity criteria during the first 4 weeks of treatment (one cycle) as the following: at least grade 2 cardiac arrhythmia, at least grade 3 non hematologic toxicity, grade 4 neutropenia lasting >7 days or any other Grade 4 hematologic toxicity, or treatment delay due to toxicity that occurred during the first cycle. No DLT was observed among the first 3 patients treated at 5, 10 and 15 mg lenalidomide/day. 9 additional subjects will be enrolled at 15 mg/day to better define the safety profile and estimate the hematologic and organ response rate. Final results regarding both toxicity and efficacy will be presented during the meeting.

Response to Bortezomib Based Induction Therapy in Newly Diagnosed Light Chain (AL) Amyloidosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1867-1867 ◽  
Author(s):  
Veerpal Singh ◽  
Ayman Saad ◽  
Jeanne Palmer ◽  
Jasleen K Randhawa ◽  
Parameswaran N. Hari
Keyword(s):  
Light Chain ◽  
Liver Dysfunction ◽  
Cardiac Involvement ◽  
Response Rate ◽  
Initial Therapy ◽  
Al Amyloidosis ◽  
Karnofsky Performance Score ◽  
Significant Activity ◽  
Newly Diagnosed ◽  
Organ Response

Abstract Abstract 1867 Poster Board I-892 Bortezomib has been shown to have significant activity in the suppression of light chain production and induction of responses in patients with relapsed refractory AL Amyloidosis. We analyzed the outcomes of 16 (9 male) newly diagnosed biopsy proven AL Amyloidosis patients treated with Bortezomib based regimens at our institution. All patients received initial therapy with Bortezomib and dexamethasone (dex). Patients with a Karnofsky performance score ( KPS) >70 received Bortezomib at starting doses of 1.3 mg/m2 along with dexamethasone 40 mg on days 1,4,8, 11 ( with a 10 day rest period). Patients with a lower KPS received Bortezomib/Dex on a weekly schedule as tolerated. Dose adjustments were made based on side effects such as neuropathy, hypotension, GI disturbances or electrolyte imbalances. Patients tolerating Bortezomib/dex with improvement in KPS had cyclophosphamide (4) or lenalidomide (1) added to their initial therapy. Patients: Median age was 64 years (39–88). Nine had kappa light chain involvement. Organ involvement was renal (73%), cardiac (63%), hepatic (25%), tongue or soft tissue (20%), GI (30%). Median KPS was 70 (50 –100). Ten of the 16 patients were treated as in-patients due to multi-organ dysfunction. Five patients required hemodialysis within a month of diagnosis. Cardiac involvement was stage 3 (Mayo risk group) in 25%. Three patients were unevaluable: 2 dying before 2 cycles and 1 discontinued therapy (Grade 3 liver dysfunction). Median follow up was 5 months (range 2–33 mo). Results: Evaluable (receiving at least 2 cycles) patients have all had a free light chain response. The overall hematological response rate was 100% with 55% partial remission (PR) and 45% complete remission (CR). Median cycles to achievement of a light chain response was 2 (range 1–4). Four patients underwent autologous stem cell transplantation with no mortality. Five (40%) of the responders have had an organ response (3 renal, 1 macroglossia, 1 cardiac) with only patients alive for >5 months having any evidence of organ response. Five (40%) of the evaluable patients have died with progressive cardiac involvement (2), relapsed disease (2) or renal failure (1) with refusal of dialysis. In patients receiving at least one dose of bortezomib, non-hematologic toxicity (>grade 2) included -neuropathy (20%), hypotension (20%), severe diarrhea (12%), sepsis (12%), paralytic ileus (6%), liver dysfunction (6%), sudden death (6%). Conclusions: Bortezomib in combination with dexamethasone has a high response rate in newly diagnosed AL amyloidosis. This regimen was well tolerated in a cohort of severe, multisystem amyloidosis patients with low treatment related mortality. Light chain responses were fast whereas organ responses were not seen prior to 5 months of therapy. The regimen also served as a platform for further intensification with the addition of lenalidomide, cyclophosphamide or autologous transplant in responders. Disclosures: Off Label Use: Bortezomib for the therapy of amyloidosis. Hari:Millenium: Honoraria, Research Funding.

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