Tackling Health System Delays for Cancer Patients in LMICs: An Innovative Multicomponent Programmatic Intervention in Botswana

Abstract 67 Background: Health system delays are a major contributor to poor outcomes among cancer patients in low- and middle-income countries (LMICs). In Botswana, while median time from cancer-related symptom onset to first presentation at local health facility is 29 days, median time to initiation of cancer treatment is 401 days. Challenges to timely diagnosis and care include clinicians' lack of knowledge, limited diagnostic capacity, poor coordination between facilities, and socioeconomic barriers of patients that impede follow-up. We sought to develop an intervention to improve access to prompt cancer care. Methods: Participating facilities are all public health facilities (21 health posts, 14 clinics, 2 hospitals) in Botswana's Kweneng-East district as well as the national referral hospital. The five components of intervention are a) training of clinicians at primary facilities on evaluation of patients with suspected cancer, b) implementation of a standardized referral algorithm for cancer suspects, c) introduction of care-coordinator role to support patient and clinician navigation of the health system, d) use of SMS-based platform to support follow-up, e) provision of transport support for vulnerable patients. The primary endpoints are stage at cancer diagnosis and time from initial presentation to initiation of cancer treatment. Evaluation of the intervention's impact will include comparing endpoints following intervention with those at baseline and those among patients residing outside the Kweneng-East district. Results: Implementation of the above multi-component intervention will be presented, including a standardized algorithm to guide the evaluation, triage and referral of patients, an intensive one-day didactic training program that adapts curricula employed in the region, and the impact of training on knowledge. Conclusion: In conducting this study, we hope to identify effective program-based measures to reduce delays and improve cancer outcomes in Botswana. These measures may be scaled to other districts, and may be applicable to similar settings in the region. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Neo M. Tapela No relationship to disclose Malebogo Pusoentsi No relationship to disclose Kerapetse Botebele No relationship to disclose Michael Peluso No relationship to disclose Isaac Nkele No relationship to disclose Jason Efstathiou Honoraria: Medivation/Astellas, Bayer Healthcare Pharmaceuticals Consulting or Advisory Role: Medivation/Astellas, Bayer Healthcare Pharmaceuticals Tomer Barak No relationship to disclose Scott Dryden-Peterson No relationship to disclose

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P3554CMR Fast-SENC intramyocardial LV & RV segmental strain helps manage cardioprotective therapy in patients exhibiting cardiotoxicity during cancer treatment

European Heart Journal ◽

10.1093/eurheartj/ehz745.0417 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H Steen ◽

M Montenbruck ◽

P Wuelfing ◽

S Esch ◽

A K Schwarz ◽

...

Keyword(s):

Breast Cancer ◽

Heart Failure ◽

Cardiac Function ◽

Cancer Treatment ◽

Cancer Patients ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

The Impact

Abstract Background Cardiotoxicity during cancer treatment has become an acknowledged problem of chemotherapy medications and radiation therapy. Limitations of biomarkers and imaging tests such as echocardiography left ventricular ejection fraction (LVEF) hinder early detection of cardiotoxicity and proactive cardioprotective therapy. Once the heart is unable to compensate for subclinical dysfunction, systemic damage and remodeling occurs increasing the potential for heart failure. Fast-SENC segmental intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) test that regionally detects subclinical intramyocardial dysfunction in 1 heartbeat. This study evaluates the ability of fSENC to detect subclinical cardiotoxicity and manage cardioprotective therapy in cancer patients. Methods This single center, prospective Prefect Study was used to evaluate cardiotoxicity and the impact of cardioprotective therapy in Breast Cancer and Lymphoma patients (NCT03543228). fSENC was acquired with a 1.5T MRI and processed with the MyoStrain software to quantify intramyocardial strain. Segmental strain was measured in three short axis scans (basal, midventricular & apical) with 16LV/6RV longitudinal segments & three long axis scans (2-, 3-, 4-chamber) with 21LV/5RV circumferential segments. fSENC CMR was performed before chemotherapy, during and after anthracycline/taxan therapy, at 1 year follow-up, and as needed in between designated follow-up periods. Cardioprotective therapy was offered to patients meeting the definition of cardiotoxicity by the ESC Guidelines on Cardiotoxicity and/or ESMO Clinical Practice Guidelines or those observing a substantial decline in cardiac function. Comparisons were made with paired t-Test with a 95% confidence interval. Results Two hundred eight (208) CMRs were performed in fifty-two (52) patients (44 female). Patients had an average (± stdev) age of 53 (15) yrs, BMI of 26 (5) kg/m2; 77% had breast cancer, 23% had Lymphoma. fSENC CMRs required 11 (2) min total exam time. Figure 1 shows bar graphs of the % of normal LV myocardium (e.g. % LV MyoStrain Segments <−17%) at baseline and sequential follow-ups for patients without cardiotoxicity and with cardiotoxicity requiring cardioprotective therapy. Patients observing cardiotoxicity had a statistically significant decline in cardiac function measured by segmental fSENC (p=0.0002) which resolved after cardioprotective therapy. Figure 1 Conclusion Segmental fSENC intramyocardial strain detects subclinical cardiotoxicity during chemotherapy and impact of cardioprotective therapy. The ability to serve as a surrogate safety endpoint for chemotherapy or other pharmacological agents, and aid management of cardiotoxicity by serving as a surrogate efficacy endpoint for cardioprotection agents, dosage, and patient compliance may help physicians detect subclinical cardiac dysfunction, and proactively manage cancer patients to avoid early or late heart failure.

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Preoperative multidisciplinary program for bariatric surgery: a proposal for the Brazilian Public Health System

Arquivos de Gastroenterologia ◽

10.1590/s0004-2803.2017v54n1-14 ◽

2017 ◽

Vol 54 (1) ◽

pp. 70-74 ◽

Cited By ~ 16

Author(s):

Elinton Adami CHAIM ◽

José Carlos PAREJA ◽

Martinho Antonio GESTIC ◽

Murillo Pimentel UTRINI ◽

Everton CAZZO

Keyword(s):

Public Health ◽

Bariatric Surgery ◽

Health System ◽

Public Health System ◽

Wound Dehiscence ◽

Pulmonary Complications ◽

Multidisciplinary Program ◽

The Impact ◽

Access To Surgery

ABSTRACT BACKGROUND Bariatric surgery has become the gold standard treatment for morbid obesity, but access to surgery remains difficult and low compliance to postoperative follow-up is common. To improve outcomes, enable access and optimize follow-up, we developed a multidisciplinary preoperative approach for bariatric surgery. OBJECTIVE To determine the impact of this program in the outcomes of bariatric surgery in the Brazilian public health system. METHODS A prospective evaluation of the individuals who underwent a preoperative multidisciplinary program for bariatric surgery and comparison of their surgical outcomes with those observed in the prospectively collected historical database of the individuals who underwent surgery before the beginning of the program. RESULTS There were 176 individuals who underwent the multidisciplinary program and 226 who did not. Individuals who underwent the program had significantly lower occurrence of the following variables: hospital stay; wound dehiscence; wound infection; pulmonary complications; anastomotic leaks; pulmonary thromboembolism; sepsis; incisional hernias; eventrations; reoperations; and mortality. Both loss of follow-up and weight loss failure were also significantly lower in the program group. CONCLUSION The adoption of a comprehensive preoperative multidisciplinary approach led to significant improvements in the postoperative outcomes and also in the compliance to the postoperative follow-up. It represents a reproducible and potentially beneficial approach within the context of the Brazilian public health system.

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The impact of COVID 19 pandemic on pattern of cancer mortality in Najran, Saudi Arabia: a single-cancer center experience

10.21203/rs.3.rs-305960/v1 ◽

2021 ◽

Author(s):

Ahmed M Badheeb ◽

Mohamed A Badheeb ◽

Hamdi A Alhakimi

Keyword(s):

Hepatocellular Carcinoma ◽

Saudi Arabia ◽

Cancer Treatment ◽

Cancer Patients ◽

Cancer Mortality ◽

Cancer Center ◽

Anti Cancer ◽

Before And After ◽

The Difference ◽

The Impact

Abstract Background: The aim of this paper is to compare the patterns and determinants of cancer mortality in Najran region before and after the COVID-19 epidemics. The association between cancer mortality and each of age, sex, site of cancer, stage, and the 30-days survival rate after the last dose of chemotherapy were assessed.Materials & Methods: Adult cancer patients who died of cancer in King Khalid Hospital in Najran Saudi Arabia, were included in this retrospective observational study. We compared mortality patterns in a period of 6 months in 2020 (March to August) with the corresponding period of 2019.Results: 50 dead adult cancer patients were included, 24 in 2019 and 26 in 2020. Among them, 21% vs 42% were younger than 65 years of age; 61% vs 62% were males, for the years 2019 & 2020 respectively. The top three killers in 2019 were colorectal, gastro-esophageal cancers, and hepatocellular carcinoma, while in 2020 were colorectal, hepatocellular carcinoma, and lymphomas. About 16.7% of patients died within 30 days of receiving anti-cancer treatment in 2019 in comparison with 7.7% in 2020. The difference in the 30-days mortality after receiving anti-cancer treatment was not statistically significant between 2019 and 2020 (p = 0.329).Conclusion: The Year 2020, the time of the COVID-19pandemic, was not associated with a significant increase in short-term mortality among patients with malignancy in Najran, Saudi Arabia. Our results generally reflect the crucial role of strict preventive national measures in saving lives and warrants further exploration.

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Initiation and Discontinuation of Complementary Therapy Among Cancer Patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.11.9651 ◽

2007 ◽

Vol 25 (33) ◽

pp. 5267-5274 ◽

Cited By ~ 13

Author(s):

Sung-Gyeong Kim ◽

Eun-Cheol Park ◽

Jae-Hyun Park ◽

Myung-Il Hahm ◽

Jin-Hwa Lim ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Initial Treatment ◽

Stage Iv ◽

Complementary Therapy ◽

Cancer Center ◽

Cumulative Probability ◽

Colorectal Cancer Patients ◽

The Impact

PurposeTo identify the initiation or discontinuation of complementary therapy (CT) and determine the impact of sociodemographic and clinical factors on CT use among cancer patients.Patients and MethodsEligible patients were age 20 or older; newly diagnosed with stomach, liver, or colorectal cancer; and started their initial treatment at the National Cancer Center, Korea, between April 1, 2001, and April 30, 2003. In total, 541 cancer patients were surveyed in face-to-face interviews at baseline, and telephone follow-up interviews were performed every 3 months for 3 years.ResultsA total of 281 patients commenced CT after diagnosis; 164 patients stopped using CT during the follow-up period. The overall cumulative probability of starting CT at 1, 2, and 3 years was 50%, 54%, and 55%, respectively. In a Cox multivariate analysis, stomach and liver cancer were associated with an increased probability of initiating CT compared with colorectal cancer. Patients who were classified as stage I, II, or III at diagnosis were associated with a decreased probability of discontinuing CT compared with stage IV.ConclusionMost cancer patients started to use CT during the initial treatment period. Thus, physicians should communicate with cancer patients about CT at this phase. In particular, more attention should be paid to women and individuals with higher household incomes because these groups are more likely to start CT.

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Demographic Characteristics and Preliminary Outcomes in a Cohort of HIV-Positive Patients With Kaposi's Sarcoma in a High ART Coverage Setting: A Report from Botswana

Journal of Global Oncology ◽

10.1200/jgo.2016.004218 ◽

2016 ◽

Vol 2 (3_suppl) ◽

pp. 70s-71s

Author(s):

Shekinah N. Elmore ◽

Elizabeth S. Bigger ◽

Mukendi K.A. Kayembe ◽

Zola Musimar ◽

Gita Suneja ◽

...

Keyword(s):

Conflicts Of Interest ◽

Kaposi Sarcoma ◽

Hiv Positive ◽

Disease Extent ◽

High Incidence ◽

Bayer Healthcare ◽

Disseminated Disease ◽

Oncologic Treatment ◽

Advisory Role

Abstract 50 Objective: Despite antiretroviral treatment coverage exceeding 90% by government estimates, Kaposi sarcoma (KS) remains the most prevalent malignancy in Botswana. Incidence has decreased minimally over the last decade. We sought to explore reasons for persistent high incidence and describe KS outcomes. Methods: Since 2010, consenting patients presenting to one of three oncology centers for KS treatment were enrolled prospectively and followed quarterly. Baseline HIV testing performed and records abstracted through April 2015. Results: 207 KS patients enrolled, 60% (125) with clinical diagnosis, 34% (71) with pathologic diagnosis, and 11 (6%) with radiologic/other diagnosis. Median age at diagnosis was 37 years (IQR: 11.9) and 63% (133) male. At presentation, 65% (134) had cutaneous and 24% (49) had disseminated disease. Revised ACTG staging was 8% (17) stage I, 54% (112) stage II, 35% (73) stage III. Nearly all, 98% (199), were HIV-infected with median nadir CD4 190 cells/μL (IQR: 208). Among HIV-infected patients, 68% (109) were not on ART at time of KS diagnosis and 26% (42) were diagnosed within first six months of ART. Of those not yet on ART, 72% (47) of men and 28% (18) of women had CD4 <250 cells/μL, p=.0004. Few cases, 6 (10%), developed in patients on ART for >6 months. Patients not on ART were referred to start. 71% (146) received chemotherapy and 7% (15) required radiation. After median follow-up 19 months, 21% (43) patients had died. Estimated 3-year OS was 76% (95% CI: 69-82%). Gender, ART duration, disease extent, and stage did not significantly predict survival. Conclusions: With high population ART coverage, KS development among individuals with CD4<250 cells/μL accounts for majority of cases referred for oncologic treatment. ART delay, particularly among men, also contributed to persistent KS burden. Overall survival with KS in Botswana is similar to US and Europe. Initiation of ART at higher CD4 thresholds is needed to control the KS epidemic. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Shekinah N. Elmore No relationship to disclose Elizabeth S. Bigger No relationship to disclose Mukendi K.A. Kayembe No relationship to disclose Zola Musimar No relationship to disclose Gita Suneja No relationship to disclose Jason A. Efstathiou Honoraria: Medivation/Astellas, Bayer Healthcare Pharmaceuticals Consulting or Advisory Role: Medivation/Astellas, Bayer Healthcare Pharmaceuticals Scott Dryden-Peterson Patents, Royalties, Other Intellectual Property: UpToDate

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A pilot examination of the impact of cancer patients' fatigue on their spousal caregivers

Palliative & Supportive Care ◽

10.1017/s1478951505050431 ◽

2005 ◽

Vol 3 (4) ◽

pp. 273-279 ◽

Cited By ~ 19

Author(s):

STEVEN D. PASSIK ◽

KENNETH L. KIRSH

Keyword(s):

Quality Of Life ◽

Cancer Patients ◽

Dyadic Adjustment ◽

Spousal Caregivers ◽

Caregiver Strain ◽

Activity Levels ◽

Small Pilot Study ◽

The Impact

Objective: In this pilot project we examined the quality of life of spouses of cancer patients who had significant fatigue.Methods: We assessed both the spouses of cancer patients and the patients who presented with chemotherapy-induced fatigue and anemia. Study endpoints included the impact that cancer patients' fatigue had on their spouses' quality of life, including their own levels of fatigue, depressive symptoms, activity levels, work absenteeism, and marital adjustment. We examined the extent to which changes in patients' fatigue from baseline to one month follow-up were associated with changes in spouses' quality of life indices.Results: 25 couples completed the study. Seven (28%) spousal caregivers reported handling fewer responsibilities at work, 8 (32%) had reduced their work hours, and 8 (32%) felt that they were less effective overall at work. Spousal caregivers also missed a significant amount of time at work during the month long study, missing an average of 2.7 (SD = 2.95) days, with an additional 1.29 (SD = 2.97) sick days and 1.76 (SD = 2.63) vacation days during that time. Spouses reporting greater levels of caregiver strain were more likely to have increased fatigue at baseline (F1,23 = 8.11, p < .01), and worse dyadic adjustment at both time points (baseline: F1,23 = 7.80, p < .01; follow-up: F1,21 = 9.24, p < .01). Also, those with more caregiver strain were less likely to engage in social activity at baseline (F1,23 = 6.11, p < .05) and more likely to engage in less work by the one month follow-up (F1,20 = 8.36, p < .01).Significance of results: Spouses who were identified as having elevated burden experienced more personal fatigue, had worse dyadic adjustment, reported poor energy levels, and tended to engage in fewer work and social activities; the impact of patient's fatigue level on these parameters was highly variable in this small pilot study.

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Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Haematological Lymphoid Malignancies: Long Term Follow-up in a Single Centre Series.

Blood ◽

10.1182/blood.v114.22.4326.4326 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4326-4326

Author(s):

Malek Benakli ◽

Redhouane Ahmed nacer ◽

Amina Talbi ◽

Rachida Belhadj ◽

Farih Mehdid ◽

...

Keyword(s):

Complete Remission ◽

Hodgkin Lymphoma ◽

Median Time ◽

Conflicts Of Interest ◽

Late Onset ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Lymphoid Leukaemia ◽

Autologous Transplant

Abstract Abstract 4326 Background Patients (pts) with recurrent and refractory haematological lymphoid malignancy (HLM) have a very limited survival expectance. RIC allo-SCT has been proposed as a strategy for retaining the graft versus malignancy effect of allo-SCT while decreasing transplant related mortality (TRM). Here, we retrospectively studied a series of 32 pts treated by RIC allo-SCT. Patients and methods Between April 2001 and November 2007, 32 pts with HLM underwent RIC allo-SCT with an HLA-identical sibling donor. Fifteen pts with multiple myeloma, 7 pts with Non-Hodgkin lymphoma, 6 pts with Chronic lymphoid leukaemia, 3 pts with Hodgkin lymphoma and 1 pt with Waldenstrom disease. At time of allo-SCT, 10 pts were in complete remission (3 received prior autologous transplant) and 22 in refractory/progressive disease (6 received prior autologous transplant). Median age was 38 years (range, 28-60) and the sex-ratio (M/F) 2,2. Median time from diagnosis to RIC allo-SCT was 18 (range,6-76) months. The conditioning regimen included Fludarabine 150mg/m2 and Melphalan 140mg/m2. GVHD prophylaxis consisted of association cyclosporine (cSA) and mycophenolate (MMF). All pts received G-CSF mobilised peripheral blood stem cells, with a median CD34+ cell count: 6,2.106/kg (range, 1.9-13,6). Results Neutropenia occurred in all pts (100%) and the median duration of aplasia was 9 (range, 5-16) days. Only 10 pts (31 %) required red blood cells transfusions and 23 pts (71 %) needed platelets transfusions. Acute GVHD was observed in 15 cases (47 %) including 10 cases of grade II-IV. Fifteen pts (75 %) had chronic GVHD, of whom 9 with an extensive form. Four pts (12 %) had CMV reactivation at a median time 60 (range, 52-80) days after transplantation. Six pts (18 %) had late onset relapse at a median time of 13 (range, 4-45) months. TRM was 43 % at one year after RIC allo-SCT. With a median follow-up of 60 (range 18-97) months, 12 pts (37,5 %) are still alive in complete remission with full donor chimerism. Twenty pts (62,5 %) have died (5 early severe infections, 10 GVHD, 3 after relapse, one myocardial infarction, and one accident). Overall and progression-free survivals at 8 years are 31 % and 30 % respectively. Conclusion This study, after a large follow-up, suggests that RIC allo-SCT is a potential therapy for refractory or progressive HLM. However, TRM is still high likely due to the inclusion of refractory and heavily pretreated pts with many comorbid conditions. Disclosures: No relevant conflicts of interest to declare.

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The Addition of Thalidomide to the Induction Treatment of Newly Presenting Myeloma Patients Increases the CR Rate Which Is Likely to Translate Into Improved PFS and OS.

Blood ◽

10.1182/blood.v114.22.352.352 ◽

2009 ◽

Vol 114 (22) ◽

pp. 352-352 ◽

Cited By ~ 8

Author(s):

Gareth J Morgan ◽

Faith E Davies ◽

Walter M Gregory ◽

Susan E Bell ◽

Alex J Szubert ◽

...

Keyword(s):

Flow Cytometry ◽

Conflicts Of Interest ◽

Residual Disease ◽

Response Rates ◽

Multiparameter Flow Cytometry ◽

Induction Treatment ◽

Overall Response ◽

Patient Pathways ◽

The Impact

Abstract Abstract 352 We present updated results from MRC Myeloma IX study evaluating the role of the addition of thalidomide to the induction and maintenance of patients with myeloma. The study ran from May 2003 – November 2007 and randomised 1,970 patients and now has a median follow up of more than 3.5 years giving it improved power to detect changes in outcome developing later after treatment. Projected median OS younger fitter patients 66 months, median OS older less fit patients 32 months. The trial comprised of 2 patient pathways, one for younger fitter patients comparing CTD (cyclophosphamide, thalidomide, dexamethasone) with CVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone), all patients going on to receive an ASCT – median age 59 years. In older less fit patients, melphalan and prednisolone (MP) was compared to CTD attenuated – median age 73 years. In both pathways following initial treatment, eligible patients were randomised to low-dose thalidomide or no maintenance. Patient's response was monitored using electrophoresis, serum free light chain and multiparameter flow cytometry. Cytogenetics was availabel on up to 60% of cases and gene expression on a subset of these. CTD is a well tolerated regimen with a good safety profile giving excellent survivals in both groups of patients despite a small increase in risk of VTE. Using modified EBMT criteria, the addition of thalidomide to induction treatment increases both response rates and depth of response for all age groups. Preliminary results as follows: overall response: CTD vs CVAD: 91% v 82%; CR 21% v 14% and 100 days post-HDM, better responses were seen in CTD with CR rates 65% v 48%. Remission depth was also greater in CTD with more patients achieving minimal residual disease negativity by flow cytometry. The addition of thalidomide increases response rates overall, and particularly complete response (CR) rates (a 17% increase in CR rates post HDM, p=.006). In older/less fit patients CTDa vs MP: overall response 83% v 46%; CR 21% v 4%. Definitive results of these analyses will be presented as well as how they translate into PFS and OS and by cytogenetic subgroup. There is a substantial increase in response with the inclusion of thalidomide but at a median follow-up of three years we are not as yet seeing a substantial increase in survival in either of the two broad patient groups. We have collected data on treatment at relapse to explore how this confounds OS data. Importantly modelling analyses indicate when and to what extent, with further follow-up, the survival differences that should accrue from this increase in CR rate are likely to translate into a survival benefit. These results have a number of important implications. We show the benefit of the addition of thalidomide to myeloma treatment but also highlight the importance of later analysis of such trials because of the emergence of significant changes at these later time points. We will present full updated results from the study including the impact of thalidomide on cytogenetic subgroups and in the maintenance setting. Disclosures: No relevant conflicts of interest to declare.

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Efficacy of Lenalidomide-Based Regimens in Multiple Myeloma Complicated by Extramedullary Plasmacytomas at Relapse or Progression.

Blood ◽

10.1182/blood.v114.22.4952.4952 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4952-4952 ◽

Cited By ~ 1

Author(s):

Jose Manuel Calvo-Villas ◽

Adrian Alegre ◽

Ricarda García-Sánchez ◽

Miguel T Hernández ◽

Pilar Giraldo ◽

...

Keyword(s):

Multiple Myeloma ◽

Median Time ◽

Light Chain ◽

Conflicts Of Interest ◽

Bone Lesions ◽

Complete Disappearance ◽

Toxicity Profile ◽

Small Series ◽

Extramedullary Plasmacytomas

Abstract Abstract 4952 Background Current clinical observations on extramedullary myeloma (EM) are based on small series of relapsed myeloma patients (pts) and, in this situation, results suggest that the disease course is often aggressive. Among novel therapies for extramedullary involvement, thalidomide has provided poor results and bortezomib is emerging as a possible useful drug. The role of lenalidomide for treatment of multiple myeloma (MM) with EM is still under investigation. Aim A multicenter retrospective study was performed by PETHEMA (Spanish Myeloma Group, Spain) to evaluate the response rate and toxicity profile of lenalidomide-based regimens in myeloma patients with extramedullary involvement at relapse or progression. All the cases were evaluated for response of MM and improvement of extramedullary plasmacytoma. Patients and Methods From October 2007 to March 2009, thirteen patients (median age 67 years; range 61–87; 7 females) treated with lenalidomide-containing regimens were recorded. Patients with bone disease without extramedullary manifestations were excluded. Response of MM was evaluated according to the new international criteria and the response of EM by measuring size changes by physical examination, CT scans and/or MR imaging. Adverse events were graded based on the WHO toxicity scale. The M-protein type was IgG in 7 cases, IgA in 5 and light chain in 1. The type of light chain was κ in 7 pts and l in 6. In eight patients the soft-tissue plasmacytomas may have developed from underlying bone lesions [(skull (n=2), rib cage (n=4) and paravertebral (n=2)], two patients had subcutaneous nodules and three had visceral involvement (liver (n=1), lung and kidney (n=1) and pleura (n=1). Multiple localizations were present in 4 pts (30.7%). Six cases (79.6%) received previous antimyeloma treatment for EM before lenalidomide therapy and the incidence of prior bone plasmacytomas was 61.5%. Median time from initial antimyeloma therapy to treatment with lenalidomide was 34 months (range 5 - 115). Median number of prior lines of chemotherapy regimens was 3 (range 1 – 4), including autologous stem cell transplantation in 2 pts, bortezomib-containing regimens in 12 (92.3%) and previous exposure to thalidomide in 1 patient. Ten pts received standard lenalidomide dose (25 mg/day every 4 weeks) plus dexamethasone (40 mg/d PO ranging from 1 to 12 doses/cycle) every 3-week; and three patients received lower doses of lenalidomide and/or different schedules. Involved-field radiotherapy was given in 2 cases. Thirty percent of patients required lenalidomide dose reduction, because of toxicity or intolerance. Results Median duration of lenalidomide treatment was 3.6 months (1 – 15). One case was not evaluable for response because of death from disease progression after one cycle. In nine out of twelve evaluable patients (75%), MM responded to lenalidomide regimens according to EBMT criteria. Three (25%) achieved complete response, five (41.6%) partial response and 1 (8.3%) minimal response. Median time to response was 63 days (range 37 – 180). Regarding EM, nine patients showed response in the size of extramedullary plasmacytomas. Seven (58.3%) achieved complete disappearance of EM and two pts reduction of the size. Response of EM was also achieved in 75% of pts previously exposed to bortezomib, and in 4/9 cases who received therapies for prior extramedullary involvement. Median follow-up period was 6.3 months (1 – 15.8). Median overall survival from the start of lenalidomide therapy was 4.7 months. At the time of analysis, seven patients were still on therapy, and ten (76.9%) were alive. Only one out of the 9 patients who had achieved a response has relapsed so far. Toxicity profile (grade 3/4) was: thrombocytopenia, 4 (30.7%); anemia, 2 (15.3%); neutropenia, 5 (46.4%); neutropenic fever, 1 (7.6%) and others, 3 (11.8%). No deep venous thrombosis (DVT) was reported. Thrombosis prophylaxis was used in most cases (92%) patients. Conclusions We report one of the first investigations specifically evaluating the activity of lenalidomide on EM. Lenalidomide-containing regimens could be an alternative promising approach to achieve clinical response in heavily treated MM patients with extramedullary disease. The duration of response and the best regimen or combination are at present unknown. These preliminary observations require further analysis and longer follow-up. Disclosures No relevant conflicts of interest to declare.

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Autologous Hematopoietic Stem Cell Transplantation (autoHSCT) in CLL: First Results of An EBMT Randomized Trial Comparing Autotransplant Versus Wait and Watch.

Blood ◽

10.1182/blood.v114.22.877.877 ◽

2009 ◽

Vol 114 (22) ◽

pp. 877-877

Author(s):

Mauricette Michallet ◽

Peter Dreger ◽

Laurent Sutton ◽

Ronald Brand ◽

Sue Richards ◽

...

Keyword(s):

Conflicts Of Interest ◽

Progression Free Survival ◽

Disease Status ◽

Primary Objective ◽

Phase Iii ◽

Induction Treatment ◽

Hematopoietic Stem ◽

Binet Stage ◽

The Impact

Abstract Abstract 877 This phase-III randomized EBMT-intergroup trial studied the impact of a consolidating autoHSCT vs no consolidation for patients with CLL in Binet stage A progressive, B or C , in CR, nodular PR or VGPR after first or second line therapy. The primary objective was to show that autoHSCT increased the 5-year progression-free survival (PFS) by 30%. Although it had been calculated that 270 patients were to be randomized, the study was terminated by the steering committee in July 2007 due to poor accrual. Here we present a first analysis based on 69% of expected follow-up forms. Results: Between November 2001 and July 2007, 223 patients were enrolled (SFGM-TC/FCLLG n=98, MRC n=62, GCLLSG n=32, SAKK n=10, other EBMT centers n=17). There were 74% males and 26% females. Binet stages were progressive A 13%, B 67%, C 20%; 59% were in CR, and 41% in very good or nodular PR. Of note, SFGM-TC/FCLLG included only patients in CR. 82% of the patients were enrolled in 1st, and 18% in 2nd remission. Patients were randomized between group 1 (autoHSCT n=112) and group 2 (observation n=111) after an induction treatment which was left at the discretion of the investigators. Median PFS was 43 months in the observation group but not reached in the autoHSCT group; 5-year PFS was 48% and 65%, respectively (p=0.005). Accordingly, autoHSCT halved the relapse risk (5-year relapse incidence 25% vs. 51%; HR 0.4 [0.23-0.71], p=0.002). Cox modeling for randomization arm, Binet stage, disease status, line of treatment, contributing group (country), and the interaction between randomization arm and contributing group confirmed that autoHSCT significantly improved PFS (HR 0.41 [0.23-0.75] p=0.004). The beneficial effect of autoHSCT was stable over all contributing groups although patients accrued by SFGM-TC/FCLLG overall had a significantly better PFS than patients from other countries (HR 0.2 [0.08-0.55], p=0.001). At 5 years, the probability of OS was 92% and 91% for autoHSCT and observation, respectively. Significant differences in terms of non-relapse death were not observed. At the last follow up, among 205 evaluable patients, 186 are alive (147CR, 39 relapse), 19 died (14 from relapse and 5 from non-relapse causes) . In conclusion, in patients with CLL in first or second remission, consolidating autoHSCT reduces the risk of progression (PFS) by more than 50%, but has no effect on overall survival. Disclosures: No relevant conflicts of interest to declare.

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