Immunological and Clinical Responses in Patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Multiple Myeloma (MM) and Chronic Lymphocytic Leukemia (CLL) after RHAMM-R3 Peptide Vaccination.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1806-1806 ◽  
Author(s):  
Jochen Greiner ◽  
Anita Schmitt ◽  
Krzysztof Giannopoulos ◽  
Jinfei Chen ◽  
Marlies Goetz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Immune Responses ◽  
Myeloid Leukemia ◽  
Hematological Malignancies ◽  
Lymphocytic Leukemia ◽  
Peptide Vaccination ◽  
Chromium Release ◽  
Clinical Responses ◽  
Acute Myeloid

Abstract We initiated a phase I/II R3 peptide vaccination for patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) overexpressing the receptor for hyaluronic acid mediated motility (RHAMM). RHAMM is a leukemia associated antigen (LAA) that is strongly expressed in several hematological malignancies and induces humoral and cellular immune responses. In this study, patients with AML, MDS, MM or CLL were included with RHAMM expression but with a limited tumor load or a minimal residual disease. To date, 25 patients were enrolled. The first 12 patients were vaccinated with 300 mcg and further patients with 1000 mcg R3 peptide emulsified with the incomplete Freund’s adjuvant. The vaccine was given four times at a biweekly interval and GM-CSF was added for five days each vaccination. Only mild drug-related adverse events were observed such as erythema and induration of the skin at the site of injection. Immunological analysis were performed using enzyme linked immunospot (ELISpot) assays for Interferon gamma and Granzyme B, tetramer staining and chromium release assays. We detected specific immune responses in 70% of patients. In most patients, we found an increase of CD8+/HLA-A2/RHAMM R3 tetramer+/CD45RA+/CCR7−/CD27−/CD28− effector T cells in flow cytometry in accordance with an increase of R3-specific CD8+ T cells in ELISpot assays. In chromium release assays, a specific lysis of RHAMM-positive leukemic blasts was shown. Moreover, we measured IL-2 and IL-10 levels in sera before and after vaccination. While IL-10 levels remained at a rather low level, we detected an increase of IL-2 in four of ten patients who showed also clinical responses. RHAMM transcripts in bone marrow and peripheral blood were quantified by real-time RT-PCR. Responding patients showed a decrease of RHAMM after vaccination. We detected positive clinical effects in several patients with myeloid disorders showing a reduction of blasts in the bone marrow. One MDS patient did not need any longer erythrocyte transfusions. Two patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunological and clinical responses. Therefore, RHAMM constitutes a promising structure for further targeted immunotherapies in patients with different hematological malignancies.

RHAMM/CD168-R3 Peptide Vaccination of HLA-A2+ Patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2781-2781 ◽  
Author(s):  
Jochen Greiner ◽  
Krzysztof Giannopoulos ◽  
Li Li ◽  
Peter Liebisch ◽  
Christiane Wendl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
T Cells ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Hematological Malignancies ◽  
Peptide Vaccination ◽  
Acute Myeloid

Abstract The receptor for hyaluronic acid mediated motility (RHAMM/CD168) has been described as a leukemia-associated antigen (LAA) eliciting both humoral and cellular immune responses in patients with hematological malignancies. RHAMM/CD168 is expressed in more than 80% of patients with acute myeloid leukemia (AML) or multiple myeloma (MM). Recently, we characterized the RHAMM/CD168-derived peptide R3 (ILSLELMKL) as a CD8+ T cell epitope. R3-primed CD8+ T lymphocytes were able to lyse autologous RHAMM/CD168+ AML blasts in a MHC class I-restricted and epitope-specific manner. Therefore, we initiated a phase I/II R3 peptide vaccination trial for patients with AML, MDS or MM overexpressing RHAMM/CD168. Patients were included with positive RHAMM/CD168 expression but with a limited tumor load. 300 mcg RHAMM R3 peptide emulsified with the incomplete Freund’s adjuvant (ISA-51, Montanide; day 3) and GM-CSF (Leukine, days 1–5) was administrated four times subcutaneously at a biweekly interval. The primary aim of the study is safety and feasibility of this peptide vaccination, secondary aims the evaluation of a specific T cell immune response to RHAMM/CD168 R3 peptide and the assessment of the influence of the R3 peptide vaccination on the remission status. Since January 2005, ten patients were enrolled in this study. The first eight patients (2 AML, 3 MDS, 3 MM) have completed the course of four vaccinations and four patients have been evaluated. The only side effects observed under R3-peptide vaccination were erythema and induration of the skin at the site of injection (CTC I°). In 2/4 patients, we found in the peripheral blood a significant increase of specific CD8+ T cells (from 0.01% to 0.8%) recognizing the R3 peptide in ELISPOT analysis and tetramer staining, one patient showed already initially a high number of HLA-A2/R3 tetramer+CCR7-CD27-CD45RA+ effector T cells and maintained this level of T cell response. Clinical responses have been assessed by the examination of peripheral blood and bone-marrow samples before and after vaccination. Patients showed a reduction of the tumor-specific expressed antigen RHAMM/CD168 in real-time RT-PCR analysis after vaccination. 2/4 patients with myeloid disorders (1 AML, 1 MDS RAEB1) showed a reduction of CD33+ cells in FACS analysis of the bone-marrow after 4 vaccinations from 10 and 7 % to 1–2 and <1%, respectively. One patient with MM showed a reduction of plasma cells in bone-marrow and a stable quantity of light chains in peripheral blood, one patient with AML showed a progressive disease. In summary, RHAMM/CD168 is a promising target antigen for immunotherapies in patients with hematological malignancies.

RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1357-1365 ◽  
Author(s):  
Michael Schmitt ◽  
Anita Schmitt ◽  
Markus T. Rojewski ◽  
Jinfei Chen ◽  
Krzysztof Giannopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Cell Epitope ◽  
Peptide Vaccination ◽  
Specific Lysis ◽  
Clinical Responses ◽  
Acute Myeloid

Abstract The receptor for hyaluronic acid–mediated motility (RHAMM) is an antigen eliciting both humoral and cellular immune responses in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). We initiated a phase 1 clinical trial vaccinating 10 patients with R3 (ILSLELMKL), a highly immunogenic CD8+ T-cell epitope peptide derived from RHAMM. In 7 of 10 patients, we detected an increase of CD8+/HLA-A2/RHAMM R3 tetramer+/CD45RA+/CCR7−/CD27−/CD28− effector T cells in accordance with an increase of R3-specific CD8+ T cells in enzyme linked immunospot (ELISpot) assays. In chromium release assays, a specific lysis of RHAMM-positive leukemic blasts was shown. Three of 6 patients with myeloid disorders (1/3 AML, 2/3 MDS) achieved clinical responses: one patient with AML and one with MDS showed a significant reduction of blasts in the bone marrow after the last vaccination. One patient with MDS no longer needed erythrocyte transfusions after 4 vaccinations. Two of 4 patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunologic and clinical responses, and therefore RHAMM constitutes a promising target for further immunotherapeutic approaches. This study is registered at http://ISRCTN.org as ISRCTN32763606 and is registered with EudraCT as 2005-001706-37.

High-Dose RHAMM-R3 Peptide Peptide Vaccination for Patients with Vaccination for Patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Multiple Myeloma (MM) and Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2911-2911 ◽  
Author(s):  
Jochen Greiner ◽  
Anita Schmitt ◽  
Krzysztof Giannopoulos ◽  
Isabel Funk ◽  
Marta Heyduk ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Residual Disease ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Clinical Effects ◽  
Peptide Vaccination

Abstract We have demonstrated immunological responses and positive clinical effects of a peptide vaccination for patients with AML, MDS, MM and CLL with a limited tumor load or a minimal residual disease over-expressing RHAMM using 300 μg RHAMM-R3 peptide (Schmitt et al., Blood 2008; Giannopoulos et al., abstract submitted). To date, 26 patients were enrolled in this clinical peptide vaccination trial. Here, we report on the second cohort of nine patients with AML, MDS and MM vaccinated with a higher peptide dose (1000 μg RHAMM-R3 peptide). The vaccine was given four times at a biweekly interval and GM-CSF was added for five days each vaccination. Similar to the patients vaccinated with 300 μg peptide only mild drug-related adverse events were observed such as erythema and induration of the skin. Immunomonitoring was performed using ELISpot assays for Interferon gamma and Granzyme B, tetramer-based flow cytometry and chromium release assays. Moreover, the frequency of regulatory T cells was quantified at different time points of vaccination. In this second cohort of patients treated with 1,000 μg peptide we detected specific immune responses in a lower frequency (4/9 patients) in contrast to patients in the 300 μg cohort (7/10 patients). In these patients with immune responses we found an increase of CD8+/HLA-A2/RHAMM-R3 tetramer+/CD45RA+/CCR7−/CD27−/CD28− effector T cells in flow cytometry in accordance with an increase of R3-specific CD8+ T cells in ELISpot assays. Two patients with positive immune responses showed a significant decrease of regulatory T cells. One patient without positive immune and clinical effects showed an increase of the frequency of regulatory T cells (5.03% to 15.9%). Three out of nine patients treated with 1,000 μg showed positive clinical effects: One patient with MDS RAEB-2 showed a reduction of leukemic blasts in the bone morrow to lower than 5%, one MDS patient achieved a normalization of the peripheral blood counts and one patient with multiple myeloma experienced a reduction of light chain in serum. The patients in the 300 μg cohort showed also a higher frequency of positive clinical effects (5 out of 10 patients). Taken together, RHAMM-R3 peptide vaccination induced both immunological and clinical responses. Therefore, RHAMM constitutes a promising structure for further targeted immunotherapies in patients with different hematological malignancies. However, higher doses of peptide do not improve the frequency and intensity of immune responses in this clinical trial.

Vaccination with the PR1 Leukemia-Associated Antigen Can Induce Complete Remission in Patients with Myeloid Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 259-259 ◽  
Author(s):  
Muzaffar H. Qazilbash ◽  
Eric Wieder ◽  
Rosa Rios ◽  
Sijie Lu ◽  
Shreya Kant ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Responses ◽  
Myeloid Leukemia ◽  
Progression Free Survival ◽  
Human Leukemia ◽  
Peptide Vaccination ◽  
Free Survival ◽  
Gm Csf ◽  
Clinical Responses ◽  
Relapsed Disease

Abstract BACKGROUND: Several studies have established the PR1 peptide (VLQELNVTV) as a human leukemia-associated antigen. PR1 is derived from proteinase 3, an aberrantly expressed protein in myeloid leukemia cells, and can be presented on HLA-A2 to cytotoxic T lymphocytes (CTL) that preferentially kill leukemia over normal hematopoietic progenitors. METHODS: Thirty-five HLA-A2+ patients with AML, MDS and CML were vaccinated with the PR1 peptide in an incomplete Freund’s adjuvant (Montanide ISA-51) and 75 mg of GM-CSF. Eligibility included AML with smoldering disease or ≥ 2nd CR, CML not responding to upfront treatment or relapsed disease, and MDS with ≥ 5% blasts. Patients were assigned at random to receive 0.25 mg, 0.50 mg, or 1.0 mg PR1 SQ every 3 weeks for 3 total injections. Immune responses (IR) were assessed by PR1/HLA-A2 tetramer staining and intracellular IFN-γ production by CTL, and clinical responses were assessed by bone marrow biopsy before study entry and 3 weeks after the 3rd vaccination. RESULTS: Thirty-five patients with a median age of 50 (26–82) were treated at a median of 26 months from time of diagnosis, and follow up was 1 to 4 years. Toxicity was limited to grade 1 and 2 injection site reactions. Overall survival was 33% at 4 years. Immune responses (IR) were elicited in 20 of 33 evaluable patients (60%). Of 16 patients with relapsed or refractory AML, there were 4 (25%) clinical responses (3 CR, 1 PR). All 4 AML patients treated during CR remain in CR. Of 10 CML patients, there was 1 cytogentic CR. Three CML patients refractory to allogeneic transplant, interferon and imatinib had stable disease with some hematological improvement since these patients were able to discontinue hydroxyurea and anagrelide. Of 5 MDS patients, there was 1 PR (17% blasts reduced to 4%). Overall survival at 4 years was 14 of 20 patients with IR vs. 0 of 13 without IR (p < 0.0001). Progression-free survival for patients with or without IR was 6.4 months vs. 2.4 months, respectively (p = 0.003). CONCLUSION: PR1 peptide vaccination is safe and can elicit both immunological and clinical responses in patients with refractory and relapsed myeloid leukemia, which improves progression-free survival of patients with IR to PR1. This is the first study to show complete molecular remission induced by peptide vaccination. These results warrant further study of immunization strategies in the treatment of leukemia.

RHAMM/CD168-R3 Peptide Vaccination of Patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM) Elicits Immunological and Clinical Responses.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 409-409
Author(s):  
Michael Schmitt ◽  
Anita Schmitt ◽  
Krzysztof Giannopoulos ◽  
Li Li ◽  
Peter Liebisch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Cell Immune Response ◽  
Target Antigen ◽  
Facs Analysis ◽  
Peptide Vaccination ◽  
Color Flow ◽  
Clinical Responses

Abstract Most patients with AML, MDS, MM and chronic lymphatic leukemia (CLL) express the receptor for hyaluronic acid mediated motility (RHAMM/CD168) on their tumor cells. We characterized RHAMM/CD168 as a leukemia-associated antigen (LAA) eliciting both humoral and cellular immune responses in patients with different hematological malignancies. CD8 positive T cells primed with the RHAMM/CD168-derived peptide R3 (ILSLELMKL) were able to lyse autologous AML blasts expressing this LAA. Therefore, we initiated a phase I/II R3 peptide vaccination to induce immunological and hematological responses for patients with AML, MDS or MM overexpressing RHAMM/CD168. Patients were included with positive RHAMM/CD168 expression but with a limited tumor load. At a biweekly interval, RHAMM R3 peptide (300 mcg for the first 12 patients and 1000 mcg for patients 13–24) emulsified with the incomplete Freund’s adjuvant (day 3) and GM-CSF (100 mcg, days 1–5) was administrated four times subcutaneously. The primary aim of the study is safety and feasibility of this peptide vaccination, secondary aims the evaluation of a specific T cell immune response to RHAMM/CD168 R3 peptide and the assessment of the influence of the R3 peptide vaccination on the remission status. Since January 2005, 14 patients have been enrolled in the study. The first ten patients (2 AML, 4 MDS, 4 MM) have completed the course of four vaccinations and have been completely evaluated. Therapy related adverse events observed under R3-peptide vaccination were erythema and induration of the skin at the site of injection (CTC I°). In 5/10 patients, we detected in the peripheral blood a significant increase of specific CD8+ T cells recognizing the R3 peptide in ELISPOT analysis and seven-color flow cytometry including tetramer staining. As expected, after vaccination with the HLA class I peptide R3 no significant increase of IgG titers against the antigen RHAMM could be detected. Clinical responses have been assessed by the examination of peripheral blood and bone-marrow samples before and after vaccination. Patients showed a reduction of the tumor-specific expressed antigen RHAMM/CD168 in real-time RT-PCR analysis after vaccination. 3/6 patients with myeloid disorders (1 AML, 2 MDS/RAEB1) showed a reduction of CD33+ cells in FACS analysis of the bone-marrow after four vaccinations from 10 and 7 % to 1–2 and &lt;1%, respectively. One patient with MDS did not need further erythrocyte substitution. Two patients with MM showed a reduction of plasma cells in the bone-marrow as by FACS analysis and of free light chains. One patient with AML and one patient with MM showed a progressive disease. Taken together, RHAMM/CD168 induced both immunological and clinical results and therefore constitutes a promising target antigen for immunotherapies in patients with hematological malignancies. Further entities with RHAMM/CD168 expression such as CLL might also be eligible for immunotherapeutic approaches using RHAMM/CD168.

A Phase I Study of CHR-2797, an Orally Active Aminopeptidase Inhibitor in Elderly and/or Treatment Refractory Patients with Acute Myeloid Leukemia or Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 443-443 ◽  
Author(s):  
Faith Davies ◽  
Gert Ossenkoppele ◽  
Pierre Zachee ◽  
Richard Noppeney ◽  
Alan Burnett ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Phase I ◽  
Active Metabolite ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Once Daily ◽  
Grade Iii ◽  
Acute Myeloid

Abstract Background. CHR-2797 is a novel, orally bioavailable agent which displays potent, tumor cell-selective, anti-proliferative properties. It is an inhibitor of Zn++-dependent aminopeptidases and generates signs of amino acid deprivation in sensitive cells, decreased protein synthesis and an increase in the level of the pro-apoptotic protein, NOXA. CHR-79888 is an active metabolite of CHR-2797. Methods. This was an open label, single agent, dose escalating phase I salvage study to assess tolerance, MTD/DLT, activity, and pharmacokinetics of CHR-2797 in patients with hematological malignancies. Elderly patients and/or relapsed patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM) were eligible. Patients were treated with escalating once daily doses (60–180 mg) for up to 84 days or until progressive disease (PD). Clinical responses were assessed by monthly bone marrow aspirates in AML/MDS patients and by M-protein levels in MM patients. Results. Sixteen adults (4 women, 12 men) of median age 70 yrs, (range 45–84 yrs) were accrued between May 2006 and Jan 2007: 13 patients with AML, 1 with MDS, and 2 with MM. Thirteen patients finished the dose finding phase of 28 days and 6 patients continued for at least 84 days. CHR-2797 was well tolerated and, except for one patient with grade III ALT elevation, no grade III/IV drug related non-hematological toxicity was observed during the first 28 days of treatment. Two patients on 180 mg developed DLT that was considered drug related: >75 percent reduction in platelet count. CHR-2797 had no influence on hemoglobin or neutrophils in this trial. Overall the most frequently reported adverse events were thrombocytopenia (6.7%), diarrhea (4.5%), dizziness (3.9%), and fatigue (3.9%). Five AML patients died in the first 3 months of the trial or within 4 weeks of discontinuing CHR-2797: 3 due to disease progression and 2 following a MI (not related to drug). Bone marrow studies revealed complete responses (< 5% blasts in bone marrow) in 3/12 AML patients after 1–3 months of therapy (60 and 130mg), one of which was also a cytogenetic response. One of the 2 responding patients on 130 mg was evaluated as a CRp at 3 months; this patient was in remission for 3 months following platelet recovery after the drug was stopped. One further AML patient (60 mg) became completely transfusion independent and remained so for 6 weeks. Good exposure to CHR-2797, including levels of the active metabolite CHR-79888 has been observed on days 1 and 28 with a terminal half life (for 79888) of 8– 11 hours. Conclusions. Oral once daily CHR-2797 in AML/MDS/MM patients with adverse prognostic risk was well tolerated. MTD for maintenance therapy was reached at 180 mg. Single agent CHR-2797 therapy showed encouraging clinical activity (incl. 3/12 CRs) in these elderly and poor risk AML patients who were able to continue therapy for at least 28 days. Because of the favorable results a phase II study with CHR-2797 in advanced AML is currently in progress.

scholarly journals High-dose RHAMM-R3 peptide vaccination for patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma

Haematologica ◽  
2010 ◽  
Vol 95 (7) ◽  
pp. 1191-1197 ◽  
Author(s):  
J. Greiner ◽  
A. Schmitt ◽  
K. Giannopoulos ◽  
M. T. Rojewski ◽  
M. Gotz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Peptide Vaccination ◽  
Acute Myeloid

scholarly journals Trends in Inpatient Chemotherapy Hospitalizations, Cost and Mortality for Patients with Hematological Malignancies: Insights from the National Inpatient Sample

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 53-54
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Kellen Gil ◽  
Brian McClune ◽  
Nausheen Ahmed ◽  
Al-Ola Abdallah ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Length Of Stay ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Hematological Malignancies ◽  
Mortality Rates ◽  
National Inpatient Sample ◽  
Inpatient Mortality ◽  
Lymphoid Leukemia ◽  
Acute Myeloid

INTRODUCTION: With the advent of newer treatment options for patients with acute leukemia and myeloma, therapies are increasingly safely administered on an outpatient basis. We hypothesized increasing utilization of outpatient options would result in decreased hospitalizations for chemotherapy, albeit with increased hospitalization charges. We interrogated chemotherapy utilization amongst adult inpatients with these malignancies using the National Inpatient Sample (NIS). METHODS: The NIS is a database providing information on all inpatient hospitalizations in the United States (US), including primary and secondary diagnoses, procedures, length of stay, and disposition. Approximately 20% of admissions are tracked, and weighted estimates are provided regarding the total number of hospitalizations in the US. Using the NIS, we tracked chemotherapy admissions for patients with the following hematological malignancies: acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and multiple myeloma (MM). Admissions for hematopoietic stem cell transplants were excluded from our analysis, and only patients aged 18 or greater were included in our analysis. Procedural International Classification of Disease (ICD) 9 and 10 codes were used to gain insight into trends of hospitalizations, elective versus urgent status, costs and length of stay for each indication. Time frame 2002-2017 was chosen as this was the most recent year for which NIS data is available. Inflation adjustments for charges were calculated based on US Department of Labor statistics. RESULTS: For MM, there were a total of 54,357 admissions for chemotherapy from 2002-2017. Amongst these admissions, 37,517 were elective, and 16,670 were non-elective, with the remainder lacking data on elective status. Figure 1 highlights trends in admissions for MM, with a significant decrease noted in the overall volume (7,547 in 2002 to 2,710 in 2014 (p=0.003)). Mortality rates for MM chemotherapy admissions, also highlighted in Figure 1, did not change significantly from 2002 to 2017 (p=0.15). Mean length of stay for chemotherapy hospitalizations increased from 4.67 days in 2002 to 6.47 days in 2017 (p&lt;0.0001). Mean inflation-adjusted hospitalization charges increased from $20,865 in 2002 to $79,161 in 2017 (p&lt;0.0001). For AML, we noted 198,288 admissions for chemotherapy from 2002-2017 of which 127,277 were considered elective, and 70,566 non-elective, with the remainder lacking data on elective status. Figure 2 highlights trends in AML admissions with a decreased volume of admissions noted from 2011 onwards after an initial increase from 2005-2008. There was a total of 14,214 admissions in 2011 compared to 10,515 in 2017 (p=0.004) There was a decrease in inpatient mortality rates from 5.5% in 2002 to 2.4% in 2017 (p&lt;0.0001). Mean length of stay was consistent during this time period from 13.35 days in 2002 to 13.34 days in 2017 (p=0.15). Mean inflation-adjusted hospitalization charges increased from $83,904 in 2002 to $133,295 in 2017 (p&lt;0.001). There was a total of 82,730 admissions for chemotherapy from 2002-2017 for ALL. Amongst these admissions, 54,565 were elective and 27,963 were non-elective, with the remainder lacking data on elective status. Figure 3 highlights trends in admissions, with an increase in number of admissions from 4,092 in 2002 to 5,960 in 2017 (p=0.86). There was a decrease in the inpatient mortality rate from 0.8% in 2002 to 0.4% in 2017 (p=0.0007). Mean length of stay stayed consistent at 7.70 days in 2002 to 7.62 days in 2017 (p=0.06). Mean inflation-adjusted hospitalization charges increased from $49,283 in 2002 to $94,787 in 2017 (p&lt;0.0001). CONCLUSIONS: There has been a steady decline in the number of admissions for inpatient chemotherapy for patients with multiple myeloma and acute myeloid leukemia over time, owing to advances in therapies delivered safely and efficaciously as an outpatient. There has also been a steady decline in inpatient mortality for chemotherapy for acute myeloid and acute lymphoid leukemia, in part due to advances in supportive care. However, the inpatient mortality rate for myeloma has not decreased, likely due to sicker patients preferentially needing admission for inpatient chemotherapy. Inflation-adjusted hospitalization charges have gone up dramatically and further work is needed to elucidate factors driving these costs, and how to mitigate them. Disclosures Ganguly: Kadmon: Other: Ad Board; Settle Genetics: Speakers Bureau; KITE Pharma: Speakers Bureau. McGuirk:Astellas: Research Funding; Novartis: Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pluristem Ltd: Research Funding; Gamida Cell: Research Funding; Bellicum Pharmaceutical: Research Funding; Fresenius Biotech: Research Funding.

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