Retrospective Analysis of Infections In An Unselected Cohort of Patients with Multiple Myeloma Treated with Lenalidomide Combinations Therapies

Abstract Abstract 5135 IMiDs exert various effects on the immune system altering cytokine production, regulating T cell costimulation and enhancing NK cell cytotoxicity. Particularly, lenalidomide is 50000 times more potent than thalidomide in inhibiting tumour necrosis factor a (TNFa), playing an important role in immune response against bacterial and virus infection. Moreover, lenalidomide causes myelosuppression, mainly neutropenia, more often than thalidomide. We assessed the incidence, type and major factors affecting infections in 127 patients with multiple myeloma (MM) receiving lenalidomide-based regimens. Median age was 67 years (range 40–88) and 53.5% were older than 65 years. Fifty-four patients (42.5%) had newly diagnosed MM whereas the remaining 73 (57.5%) had relapsed/refractory disease. Among this group, 67% of patients had previous received more than one line of therapy and 26% had undergone APSCT. ISS stage 2–3 and renal failure were recognized in 54.5% and 8.5% of patients, respectively, and 15% of them had a ECOG PS >= 2. Eighty patients (63%) received lenalidomide plus dexamethasone and 47 (37%) lenalidomide combined with steroids and chemotherapy. Median courses of lenalidomide administered was 6 (range 1–28). Nearly all patients (95%) received trimethoprim-sulfamethoxazole (TMP-SMZ) as prophylaxis for infections and granulocyte-colony stimulating factor was used according to guidelines. Twenty-six patients (20.5%) developed infections resulting of grade 1–2 in 8 patients (6%) and 3–5 in the remaining 18 (14%). There were two deaths (1.5%) due to infections. Type of infection were: pneumonia in 15 (58%), upper respiratory tract infections in 3 (11.5%), FUO in 3 (11.5%), septic shock by gram-negative microorganisms in 2 (8%), cholecystitis in 2 (8%) and VZV infection in one (4%). Risk of grade 3–5 infection was 16% at 12 months; 62.5%, 69% and 94% of infections occurred at 3, 4 and 6 months, respectively. Univariate analysis showed that ISS 2–3 (16.5% vs 7%; p=0.017), creatinine > 2 mg/dl (23.5 vs 10.5%; p=0.087) and WBC < 4000/mcl (33% vs 12.7%: p=0.087) prior therapy were associated with development of severe infection, whereas all other variables as sex, age, PS, disease status, monoclonal component level, thrombocytopenia prior therapy, renal failure, type of therapy and number of prior lines of therapy did not affect infections. Multivariate analysis selected only ISS as factor affecting severe infection development. Particularly, the risk of grade 3–5 infections at 6 months was 18% in patients with ISS 2–3 if compared with 6% in those with ISS 1 (p=0.034). As regard outcome parameters, there was a trend for a longer PFS in patients without infection (median PFS = 8 vs 16 months in patients without infections; p=0.064); however, OS of patients developing infection was significantly shorter compared to that of patients who did not develop infections (median OS=26 vs 33 months; p=0.001). Multivariate analysis showed that infections significantly affected OS (HR=3.2; 95%CI=1.5–6.7; p=0.002) adjusted for age, PS, ISS, renal function and therapy with 2 or 3 drugs. In clinical practice, infections represent a frequent complication in patients with MM receiving lenalidomide-based regimens, as reported in phase II-III trials. Respiratory infections accounted for a large majority (nearly 70%), although severe gram-negative septic shock should be taken into account in neutropenic patients. Nearly all patients who developed infections during the first 6 months of therapy and those with higher tumour burden have been found to be at higher risk. In conclusion, a broader antibiotic prophylaxis (ie TMP-SFZ plus fluoroquinolones) should be taken into consideration to prevent severe infections and ameliorate final outcome of patients treated with lenalidomide. Disclosures: Caravita: Celgene: Honoraria, Research Funding; Janssen: Honoraria. Offidani:Celgene: Honoraria. Gentili:celgene: Honoraria.

Download Full-text

Pembrolizumab in Combination with Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma (RRMM)

Blood ◽

10.1182/blood.v128.22.490.490 ◽

2016 ◽

Vol 128 (22) ◽

pp. 490-490 ◽

Cited By ~ 13

Author(s):

Ashraf Z Badros ◽

Elizabeth Hyjek ◽

Ning Ma ◽

Alexander M. Lesokhin ◽

Aaron P. Rapoport ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

Plasma Cells ◽

Cell Function ◽

Conflicts Of Interest ◽

Upper Respiratory Tract ◽

T Cell Therapy ◽

Prior Therapy ◽

Grade 3 ◽

Tract Infections

Abstract BACKGROUND: Immunotherapy in MM is emerging as an effective modality in therapy of MM with the approval of several monoclonal antibodies and encouraging results for vaccines and T cell therapy. Programmed death 1 (PD-1) receptor and its ligand (PD-L1) is one mechanism of immune evasion by MM to suppress T cell function. In this trial, we hypothesized that pembrolizumab, a PD-1-blocking antibody, would enhance immune modulatory properties of pomalidomide in RRMM pts. METHODS: In this single center, phase II study, 48 patients with RRMM received 28-day cycles of pembrolizumab (at a dose of 200 mg IV) every 2 weeks (in a run in phase, first 6 patients received 200 mg IV every 4 weeks) plus pomalidomide (4 mg daily x 21 days) and dexamethasone 40 mg weekly. Study objectives were measurements of safety & efficacy and correlation of the CD3/PD-1 on T cells and PD-L1 on plasma cells with response. RESULTS: The median age was 64 years (range: 35-82); 38% were black and 65% were men, Patients had a median of 3 lines of prior therapy (range: 2-6); All patients had received both IMids and Proteosome inhibitors; 70% had prior auto-SCT. 80% were double refractory to both IMids (lenalidomide) and Proteosome inhibitors [bortezomib (n=18) or carfilzomib (n=20)] and an additional 20% were refractory to lenalidomide. The median time from MM diagnosis to study entry was 4 years (range: 1-25). Most common cytogenetic abnormalities were 1q+ (60%), hyperdiploidy (15%) and high-risk FISH [del 17p, t(4:14) and/or t(14:16)] in 38%. Six patients had soft tissue extramedullary plasmacytomas. There were no infusion-related reactions. Hematologic toxicities (≥ grade 3) were anemia (21%), neutropenia (40%), lymphopenia (15%) and thrombocytopenia (8%). Non-hematologic events Grade ≥3 were fatigue (15%), hyperglycemia (25%), upper respiratory tract infections (21%), rash (10%); and most frequent grade ≥2 were dyspnea (54%), dizziness (44%), increased creatinine 38%, edema (35%), rash (30%), constipation 30%) and arrhythmias (19%). Events of clinical significance, autoimmune mediated, included interstitial pneumonitis (13%), hypothyroidism (10%), transaminitis(6%), adrenal insufficiency (4%) and vitiligo (2%). Nine pts had pomalidomide dose reductions due to rash, neutropenia, palpitations and fatigue; one pt reduced pembrolizumab for pneumonitis. At a median follow up of 10 months (range: 2-18): 25 pts continue on the study and 23 pts discontinued therapy due to disease progression (n= 15), side effects (n=7) and protocol violation (n=1). Five pts died while on study due to progressive disease (n=3), sepsis (n=1, sAE), and one from a cardiac event. Three additional pts died off therapy. On intent to treat analysis; the overall response rate (ORR) with ≥ Partial response were observed in of 27 of 48 pts (56%) including: sCR (n=4, 8%), nCR (n=3, 6%), VGPR (n=6, 13%), PR (n=14, 29%). Additionally, 7 pts (15%) had minimal response, 9 (19%) had stable disease, 2 progressed and 3 were not evaluable for response. Of 38 double refractory pts ORR was 55% including, sCR (n=2, 5%), nCR (n=2, 5%), VGPR (n=4, 10%) and PR (n=13, 27%). Of 18 high-risk pts ORR was 33% including VGPR (n=2, 11%) and PR (n=4, 22%). Median duration of response for responding pts was 8.8 months and for pts ≥ VGPR, DOR was 10.7 months. Correlation of PD-1 and PD-L1 expression and response will be presented. CONCLUSION: Pembrolizumab, pomalidomide and dexamethasone shows promising durable therapeutic activity and an acceptable safety profile in RRMM pts. ClinicalTrials.gov number, NCT02289222 Disclosures No relevant conflicts of interest to declare.

Download Full-text

Lymphocytopenia Is Associated with an Increased Risk of Severe Infections in Patients with Multiple Myeloma Treated with Bortezomib-Based Regimens

Blood ◽

10.1182/blood.v120.21.5042.5042 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5042-5042 ◽

Cited By ~ 1

Author(s):

Sung-Hoon Jung ◽

Jae-Sook Ahn ◽

Seung-Ji Kang ◽

Deok-Hwan Yang ◽

Yeo-Kyeoung Kim ◽

...

Keyword(s):

Multiple Myeloma ◽

Multivariate Analysis ◽

Conflicts Of Interest ◽

Severe Infection ◽

Infectious Complications ◽

P Value ◽

Factors Affecting ◽

Increased Risk ◽

Severe Infections ◽

Grade 3

Abstract Abstract 5042 Bortezomib is a proteasome inhibitor with potent antimyeloma activity in relapsed/refractory multiple myeloma (MM) patients. We evaluated the type and factors affecting the onset of infectious complications and mortality owing to infection in MM patients treated with bortezomib-based regimens. We reviewed 139 patients with MM treated with regimens containing bortezomib in order to assess the type and factors affecting the development of severe infections. Infections occurred in 56 (40. 3%) of 139 patients and 83 (7. 8%) cases of the 1, 069 evaluable cycles. Severe infections developed in 43 (30. 9%) patients and ten patients (7. 1%) died during bortezomib-based treatment. Multivariate analysis determined lymphocytopenia grade 3–4 (OR 3. 17, 95% CI 1. 38–7. 31, p = 0. 007) and number of cycle ° Â 8 cycles (OR 3. 91, 95% CI 1. 39–11. 02, p =0. 010) as risk factors associated with increased severe infection. This study showed that MM patients who received bortezomib-based regimens are at a higher risk of severe infections within eight cycles of treatment during especially severe lymphocytopenic period. MM patients treated with bortezomib-based regimens should be closely monitored for the development of infectious complications during lymphocytopenia. Table I. Multivariate analysis of factors affecting severe infection development Parameter OR (95% CI) p-Value Age (> 65) 1.78 (0.77–4.13) 0.180 Immunophenotype IgA 1.51 (0.60–3.77) 0.379 Lymphocytopenia (grade 3–4) 3.17 (1.38–7.31) 0.007 Neutropenia (grade 3–4) 1.25 (0.55–2.85) 0.600 Number of cycles (°Â 8 cycles) 3.91 (1.39–11.02) 0.010 Disclosures: No relevant conflicts of interest to declare.

Download Full-text

A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma

Leukemia ◽

10.1038/s41375-020-0857-2 ◽

2020 ◽

Vol 34 (12) ◽

pp. 3298-3309 ◽

Cited By ~ 4

Author(s):

Joseph Mikhael ◽

Joshua Richter ◽

Ravi Vij ◽

Craig Cole ◽

Jeffrey Zonder ◽

...

Keyword(s):

Multiple Myeloma ◽

Single Agent ◽

Proteasome Inhibitors ◽

Progression Free Survival ◽

Dose Finding ◽

Upper Respiratory Tract ◽

Phase 2 ◽

Refractory Multiple Myeloma ◽

Prior Therapy ◽

Tract Infections

AbstractA Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ≥3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38–85), 5 (2–14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg Q2W/Q4W, 10 mg/kg Q2W, and 20 mg/kg QW/Q2W, respectively. At doses ≥10 mg/kg, median progression-free survival and overall survival were 4.6 and 18.7 months, respectively, and the ORR was 40.9% (9/22) in patients with high-risk cytogenetics. CD38 receptor density was similar in responders and non-responders. The most common non-hematologic adverse events (typically grade ≤2) were nausea (34.0%), fatigue (32.0%), and upper respiratory tract infections (28.9%). Infusion reactions (typically with first infusion and grade ≤2) occurred in 51.5% of patients. In conclusion, isatuximab is active and generally well tolerated in heavily pretreated RRMM, with greatest efficacy at doses ≥10 mg/kg.

Download Full-text

Melioidosis with Septic Shock and Disseminated Infection in a Neutropenic Patient Receiving Chemotherapy

Case Reports in Infectious Diseases ◽

10.1155/2020/8976180 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Sitthi Sukauichai ◽

Chantana Pattarowas

Keyword(s):

Septic Shock ◽

Mortality Rate ◽

Burkholderia Pseudomallei ◽

Neutropenic Patient ◽

Pulmonary Nodules ◽

Severe Infection ◽

Gram Negative ◽

Negative Bacillus ◽

Gram Negative Bacillus ◽

Chemotherapy Induced Neutropenia

Melioidosis is a bacterial infection, caused by Gram-negative bacillus, Burkholderia pseudomallei, widespread in Southeast Asia and the northern part of Australia, resulting in a high mortality rate in severe infection. However, it has rarely been reported in patients with chemotherapy-induced neutropenia. The authors described a case of melioidosis in a neutropenic patient presenting with septic shock after receiving chemotherapy. Blood and urine cultures were positive for Burkholderia pseudomallei, and CT scan showed multiple pulmonary nodules and hepatosplenic abscesses. The patient was successfully treated with antibiotics for the infection and with combined modalities for a malignancy.

Download Full-text

Multiple myeloma complicated with pseudomonas endocartiditis

Einstein (São Paulo) ◽

10.1590/s1679-45082012000400017 ◽

2012 ◽

Vol 10 (4) ◽

pp. 498-501 ◽

Cited By ~ 4

Author(s):

Juliana Todaro ◽

Patrícia Weinschenker Bollmann ◽

Amit Nussbacher ◽

Luis Fernando Aranha Camargo ◽

Bento Fortunato Cardoso dos Santos ◽

...

Keyword(s):

Multiple Myeloma ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Rare Case ◽

Morbidity And Mortality ◽

Infectious Agents ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Tract Infections

Patients diagnosed with multiple myeloma are more susceptible to infections which are the major causes of morbidity and mortality associated to this disease. The main infectious agents involved are Gram-positive bacteria. However, after chemotherapy an increase in the incidence of Gram-negative strains is observed. These bacteria are also responsible for most cases of urinary tract infections. Here is reported a rare case in a 73-year-old man with multiple myeloma who developed endocarditis due to pseudomonas.

Download Full-text

Expanded Access Program (EAP) for Lenalidomide (Revlimid®) Plus Dexamethasone in over 1400 Subjects with Relapsed or Refractory Multiple Myeloma.

Blood ◽

10.1182/blood.v108.11.3556.3556 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3556-3556 ◽

Cited By ~ 2

Author(s):

Christine Chen ◽

Donna E. Reece ◽

David Siegel ◽

Ruben Niesvizky ◽

Ralph Vincent Boccia ◽

...

Keyword(s):

Multiple Myeloma ◽

Phase Iii ◽

Advocacy Groups ◽

Refractory Multiple Myeloma ◽

Expanded Access ◽

Prior Therapy ◽

Expanded Access Program ◽

The Us ◽

Grade 3 ◽

Access Program

Abstract Background: Lenalidomide (Revlimid®) in combination with dexamethasone was approved in the US on June 29, 2006 for the treatment of subjects with multiple myeloma who had received at least one prior therapy. On February 28, 2005 based upon a positive interim analysis of two pivotal placebo-controlled Phase III studies, an independent Data Safety Monitoring Board recommended the studies be unblinded and all subjects in both studies be given access to lenalidomide. In April 2005, the FDA in association with myeloma patient advocacy groups requested Celgene establish an expanded access program to make lenalidomide plus dexamethasone available to subjects with relapsed or refractory multiple myeloma while the treatment was awaiting approval. Aim: To provide lenalidomide to multiple myeloma subjects with a high likelihood of benefit and to obtain additional safety data. Methods: Subjects with relapsed or refractory multiple myeloma that received at least 1 prior therapy were eligible. Subjects received 25 mg lenalidomide plus high-dose dexamethasone in 4-week cycles until disease progression was documented, study drug was discontinued, or lenalidomide became commercially available for this indication. Results: Between September 8, 2005 and July 25, 2006, approximately 1400 subjects in the US and Canada were enrolled into the study. A data snapshot taken March 17, 2006 demonstrated that 746 subjects had been enrolled, median age was 63 years, 60% were male, and 66.5% had Stage III disease. Median time on study was 7.1 weeks (0.1–24.4) and median daily dose was 20.5 mg. At least one Grade 3 or 4 adverse event was reported in 261 (35%) of the 746 subjects. Most commonly reported Grade 3–4 events were neutropenia (7.9% of subjects), thrombocytopenia (6.0%), fatigue (3.6%), anemia (3.5%), pneumonia (3.1%) and hyperglycemia (2.0%). These most commonly reported Grade 3–4 adverse events were the same as those found in the previous pivotal studies, however, their frequencies of occurrence were lower in the current study probably due to ongoing data collection and differences in study maturity. Likewise, the most commonly reported adverse events (all grades) were the same as those reported in the two previous pivotal studies. Conclusion: Preliminary data from this expanded access program in over 1400 subjects with multiple myeloma are consistent with results from two earlier Phase III pivotal studies. The EAP of lenalidomide plus dexamethasone in multiple myeloma represents a model of how government, advocacy groups, healthcare providers and industry can work together to quickly provide treatment to subjects in need while a clearly active treatment regimen is awaiting approval.

Download Full-text

Phase I-II Trial of Oral Cyclophosphamide, Prednisone and Lenalidomide (Revlimid®) (CPR) for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma

Blood ◽

10.1182/blood.v116.21.3055.3055 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3055-3055

Author(s):

Donna E. Reece ◽

Esther Masih-Khan ◽

Arooj Khan ◽

Saima Dean ◽

Sharon Fung ◽

...

Keyword(s):

Multiple Myeloma ◽

Dose Level ◽

Research Funding ◽

Response Rate ◽

Objective Response ◽

Median Number ◽

Prior Therapy ◽

Best Response ◽

Level 3 ◽

Grade 3

Abstract Abstract 3055 Lenalidomide (Revlimid®) and dexamethasone is an effective regimen for relapsed/refractory (rel/ref) multiple myeloma (MM) patients (pts) with an overall response rate of 60% and median time to progression of 13.4 months (Dimopoulos ME, et al. Leukemia 2009; 23: 2147-52). We combined lenalidomide with the alkylating agent combination of cyclophosphamide and prednisone—an older regimen with minimal cumulative myelosuppression and good activity as second or third line therapy (Trieu Y, et al, Mayo Clin Proc 2005; 80: 1582). The CPR regimen consisted of cyclophosphamide (CY) on days 1, 8, and 15, lenalidomide on days 1–21 and prednisone 100 mg q 2 days in a 28-day cycle. ASA 81 mg/day was given as DVT prophylaxis. Three dose levels were evaluated using a 3 × 3 dose escalation design. Thirty-two pts were entered between 11/2007-06/2009; median age was 64 (42-80) yrs, 60% were male, and immunoglobulin isotype was IgG in 19 (62%), IgA in 8 (25%) and light chain in 4 (13%) pts. Median β2-microglobulin level was 257 (92-767) nm/L, albumin 39 (34-48) g/L, creatinine 83 (50-126) μmol/L, platelet count 355 (75-479) × 109/L and ANC 2.5 (1.1-6.1) × 109/L. The median number of prior regimens was 2 (1-5). Prior therapy included: ASCT (single in 91%; double in 19%), thalidomide (28%) and bortezomib (50%). FISH cytogenetics were available in 13 pts; 1 had del 13q but none had t(4;14) or del p53. Table 1 summarizes protocol treatment delivered. Table 1. Dose level N Cyclophosphamide dose (mg/m2) Lenalidomide dose (mg) Prednisone dose (mg) Median # cycles given 1 3 150 15 100 12 (12–34+) 2 3 150 25 100 10 (9–23) 3 26 300 25 100 17 (5–28+) 1–3 (All) 32 150–300 15–25 100 19 (5–34+) Dose limiting toxicity was not observed during cycle 1 at any dose level. Grade 3–4 toxicities during the trial included: thrombocytopenia in 7 (22%) and neutropenia in 9 (29%), managed with dose reduction and/or growth factors; five episodes of febrile neutropenia occurred, all at dose level 3. In cohort 3, other grade 3–4 non-hematologic toxicities included 1 episode each of abdominal pain/bacteremia, hypokalemia, fatigue, sick sinus syndrome, cardiac amyloidosis, perforated diverticulum and 2 episodes of DVT. Two heavily pretreated pts developed 2° MDS, including 1 previously treated for lymphoma, 43 and 190 mos after the diagnosis of MM. The best response using modified EBMT criteria was documented at a median of 7 (1-26) cycles and included the following: dose level 1 (1 CR, 2 PR); dose level 2 (1 VGPR, 2 PR); dose level 3 (4 CR, 14 VGPR, 11 PR, 1 MR and 1 stable disease). At a median F/U of 16 (5-34) months, 13 pts remain on study and 18 have progressed at a median of 10 (2-23) mos; 1 was lost to F/U and 9 have died of progressive MM. The 1-year actuarial OS and PFS rates are 93% (95% CI 76–98%) and 78% (95% CI 60–89%), respectively. We conclude: 1) the combination of full doses of the agents in CPR can be given in a 28 day cycle with an acceptable safety profile; 2) the objective response rate (CR + PR + MR) in all 32 pts to date is 94%; 3) the 1-year OS of 93% and PFS of 78% compare favorably with other 3-drug combinations in rel/ref MM pts; 4) further evaluation of this regimen in newly diagnosed pts would be of interest. Disclosures: Reece: Celgene: Honoraria, Research Funding. Off Label Use: Combination of lenalidomide and cyclophosphamide and prednisone in relapsed and refractory myeloma patients. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

Download Full-text

Combined Bendamustine, Prednisone and Bortezomib (BPV) In Patients With Relapsed Or Refractory Multiple Myeloma and Light Chain Induced Renal Failure

Blood ◽

10.1182/blood.v122.21.3203.3203 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3203-3203 ◽

Cited By ~ 1

Author(s):

Wolfram Pönisch ◽

Barbara Moll ◽

Dietger Niederwieser

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Renal Dysfunction ◽

Light Chain ◽

Severe Side Effect ◽

Renal Response ◽

Group A ◽

Severe Renal Dysfunction ◽

Grade 3 ◽

Group B

Abstract Introduction Serious renal failure represents a main complication of Multiple Myeloma (MM). An estimated 25% to 50% of patients are affected during the course of their disease. These patients are at increased risk for infections and have a significantly worse prognosis. Small phase I/II studies suggest that treatment with chemotherapy and/or new substances results in recovery of renal function in more than 25%. The window of opportunity for reversal of renal impairment is rather small making an immediate and highly active treatment strategy mandatory. Bortezomib and bendamustine have turned out to be quickly acting and effective drugs in the treatment of MM. Methods Between March 2005 and March 2013, 36 patients (median age 64; range 32-81 years) with relapsed/refractory MM and light chain induced renal failure (creatinine clearance <60ml/min) were treated with bendamustine 60mg/qm on day 1 and 2, bortezomib 1.3mg/qm on day 1, 4, 8 and 11, and prednisone 100mg on day 1, 2, 4, 8 and 11. Cycles were repeated every 21 days. Patients were divided into two groups: group A (n=20) consisted of patients with moderate or severe renal dysfunction (eGFR 15-59ml/min) and group B (n=16) of patients with renal failure/dialysis (eGFR <15ml/min). Results The median number of the BPV-treatment was 2 (1-7) cycles. 24 patients (67%) responded after at least one cycle of chemotherapy with 3 CR, 3 nCR, 6 VGPR, and 12 PR. Six patients had MR, 2 patients stable disease and 4 patients had a progress. With a median follow up of 22 months of the surviving patients, median PFS and OS for patients with moderate or severe renal dysfunction (group A) were 10 months and 25 months, respectively. Outcome for these patients was significantly better compared to patients with renal failure/dialysis (group B) with a median PFS and OS of 3 months and 7 months, respectively (p<0.02). Eleven patients showed a CRrenal, 5 patients a PRrenal and 15 patients a MRrenal. Median time to first renal response and best renal response were 21 days and 42 days, respectively. The most common severe side effect was grade 3-4 thrombocytopenia in 81% of the patients. Grade 3-4 neutropenia was observed in 50% of the patients. Moderate to severe infections were seen in 13 patients. Summary These results indicate that the combination of bortezomib, bendamustine and prednisone is effective and well tolerated in patients with relapsed/refractory MM and light chain induced renal failure. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Deteksi Bakteri pada Ibu Hamil dan Post Partum Di Kabupaten Mamuju

Jurnal Penelitian Kesehatan SUARA FORIKES (Journal of Health Research Forikes Voice) ◽

10.33846/sf11nk112 ◽

2019 ◽

Vol 11 ◽

pp. 58

Author(s):

Ashriady Ashriady ◽

Abbas Mahmud ◽

Nurdiana Nurdiana

Keyword(s):

Pregnant Women ◽

Post Partum ◽

Enterobacter Aerogenes ◽

Severe Infection ◽

Acinetobacter Calcoaceticus ◽

Observational Research ◽

Early Screening ◽

Gram Negative ◽

Common Causes ◽

Tract Infections

Causes of non-obstetric sepsis in pregnant women include malaria, HIV and pneumonia. Urinary tract infections are often linked as the most common cause of infection in pregnancy. Common causes of sepsis are gram-negative bacteria such as Acinetobacter calcoaceticus, Enterobacter aerogenes, Pseudomonas sp and Eschericia coli. High risk for pregnant women is a condition of deviation from normal which directly causes morbidity and death of both mother and baby breech location in premigravida, severe infection/sepsis, preterm labor. Based on this description, researchers were interested in screening bacteria in pregnant women with sepsis in Mamuju Regency in West Sulawesi Province. The purpose of this study was to detect the presence of bacteria in pregnant women in Mamuju Regency. This type of research is descriptive observational research. The time of the study is in the months of May to November 2019. The population was all pregnant women who visit the PKM and/or Hospital in Mamuju Regency, taken using the accidental Sampling method. The results showed a bacterial infection with gram-negative (rod) and gram-positive (round) types in pregnant women. Early detection of the incidence of infection and the cause of the infection is still needed so the researchers recommend that early screening be done on pregnant women. This research can be continued with various specimens such as sputum or wound swabs in women with caesarean section. Keywords: pregnant women; infections; bacteria; gram negative

Download Full-text

Cedecea lapagei An Extremely Rare Uropathogen: A Case Report and Review of the Literature

10.21203/rs.3.rs-181472/v1 ◽

2021 ◽

Author(s):

Abdikarim Hussein Mohamed ◽

Hussein Ali Mohamud

Keyword(s):

Renal Failure ◽

Case Report ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Beta Lactam ◽

Gram Negative ◽

Beta Lactamases ◽

Extended Spectrum ◽

Extended Spectrum Beta Lactamases ◽

Tract Infections

Abstract Background: Gram-negative enterobacteria are the most common cause of urinary tract infections. Cedecea is a new separate genus in the family enterobacteriaceae, and it is a very rare pathogen that was primarily found in the respiratory tract. Cedecea lapagei is a very rare pathogen of urinary tract infections. To the best of our knowledge, this is the first case report in the world reported in English literature. Case presentation: A 55 years old man with chronic renal failure, poorly controlled diabetes mellitus, and hypertension presented with acute exacerbations of renal failure and irritative voiding symptoms. After stabilization and empirical antibiotic therapy with Ceftriaxone, the patient’s condition was not improved and deteriorated progressively. After the request of urine culture, the culture was isolated, an extremely rare uropathogen recently recognized by the Centers for Disease Control and Prevention (CDC); the Cedecea lapagei. Cedecea lapagei identification had been done using Eosin methylene blue agar (EMB). Gram-negative lipase positive bacteria with bacillus in shape, motile in nature that is non-spore-forming, and non-encapsulated enterobacteria with the final result of >100,000 colony-forming units per ml of Cedecea lapagei were isolated. Mueller-Hinton agar had been used to perform antimicrobial sensitivity and resistance. The pathogen was extensively resistant to the extended-spectrum beta-lactamases antibiotics and extended-spectrum beta-lactam inhibitors while carbapenems, fluoroquinolones, aminoglycosides, and Trimethoprim-sulfamethoxazole showed a higher sensitivity rate. Conclusion: The treatment of Cedecea lapagei infections represents a challenging issue due to its multi-drug resistant and extensive drug resistance patterns to a variety of antimicrobial classes, such as extended-spectrum beta-lactamases, cephalosporins, and beta-lactam inhibitors. Antimicrobial treatment should be aligned with the culture findings once available.

Download Full-text