scholarly journals Glucocorticoid-induced osteoporosis: presentation and comments on the new American College of Rheumatology guidelines

2018 ◽  
Vol 20 (3) ◽  
pp. 114-120
Author(s):  
Natalia V. Toroptsova
Keyword(s):  
Age Groups ◽  
Organ Transplant ◽  
Osteoporotic Fractures ◽  
High Dose ◽  
Mineral Density ◽  
First Line ◽  
American College Of Rheumatology ◽  
Over 40 Years ◽  
Very High

The article presents a review of the clinical guidelines of 2017 American College of Rheumatology for prevention and treatment of glucocorticoid-induced osteoporosis. The guidelines i contain fracture risk gradation not only for people over 40 years , based on the measurement of bone mineral density, 10-year probability of fractures by FRAX and prior osteoporotic fractures, but also for people under 40 years. The guidelines present , recommendations for initial and follow-up treatment for prevention of glucocorticoid-induced osteoporosis according the level of risk of fractures in different age groups of adults, and in children from 4 years of age, in patients with organ transplant and patients older than 30 years, receiving very high-dose of glucocorticoids . Oral bisphosphonates were recommended as first line treatment due to safety, cost, and because of lack of evidence for superior antifracture benefits from other OP medications. Oral bisohosphonates could be switched to another medication in case of intolerance. The issues of applicability of these recommendations in national clinical practice are being discussed.

scholarly journals Anxiety Levels Predict Bone Mineral Density in Postmenopausal Women Undergoing Oral Bisphosphonates: A Two-Year Follow-Up

2021 ◽  
Vol 18 (15) ◽  
pp. 8144
Author(s):  
Gabriella Martino ◽  
Federica Bellone ◽  
Carmelo M. Vicario ◽  
Agostino Gaudio ◽  
Andrea Caputo ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Rating Scale ◽  
Osteoporotic Fractures ◽  
Oral Bisphosphonates ◽  
Mineral Density ◽  
X Ray ◽  
Hamilton Anxiety Rating Scale ◽  
Anxiety Levels

Clinical psychological factors may predict medical diseases. Anxiety level has been associated with osteoporosis, but its role on bone mineral density (BMD) change is still unknown. This study aimed to investigate the association between anxiety levels and both adherence and treatment response to oral bisphosphonates (BPs) in postmenopausal osteoporosis. BMD and anxiety levels were evaluated trough dual-energy X-ray absorptiometry and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Participants received weekly medication with alendronate or risedronate and were grouped according to the HAM-A scores into tertiles (HAM-A 3 > HAM-A 2 > HAM-A 1). After 24 months, BMD changes were different among the HAM-A tertiles. The median lumbar BMD change was significantly greater in both the HAM-A 2 and HAM-A 3 in comparison with the HAM-A 1. The same trend was observed for femoral BMD change. Adherence to BPs was >75% in 68% of patients in the HAM-A 1, 79% of patients in the HAM-A 2, and 89% of patients in the HAM-A 3 (p = 0.0014). After correcting for age, body mass index, depressive symptoms, and the 10-yr. probability of osteoporotic fractures, anxiety levels independently predicted lumbar BMD change (β = 0.3417, SE 0.145, p = 0.02). In conclusion, women with higher anxiety levels reported greater BMD improvement, highlighting that anxiety was associated with adherence and response to osteoporosis medical treatment, although further research on this topic is needed.

Preliminary Results of a Prospective Randomized Study Comparing First Line Conventional Therapy Versus High Dose Therapy with Autologous CD34+ Purified Progenitor Cell Support in B CLL Patients with B and C Binet Stages: The GOELAMS LLC98 Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 152-152 ◽  
Author(s):  
Annie Brion ◽  
Beatrice Mahe ◽  
Brigitte Kolb ◽  
Bernard Audhuy ◽  
Philippe Colombat ◽  
...  
Keyword(s):  
Stem Cell ◽  
Skin Cancer ◽  
Disease Progression ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
Stem Cell Support ◽  
Dose Therapy ◽  
Cell Support

Abstract The role of high dose chemotherapy with autologous stem cell support in first line therapy in patients with B-CLL remains to be defined. The aim of the prospective randomized GOELAMS LLC 98 (Groupe Ouest Est d’etude des Leucemies et Autres Maladies du Sang) trial was to compare two therapeutic strategies in previously untreated B-CLL patients younger than 60 years with B and C Binet stages. Conventional chemotherapy (Arm A) consisted of six monthly courses of CHOP, (i.e. vincristin IV 1 mg/m2 on day 1, doxorubicin IV 25 mg/m2 on day 1, cyclophosphamide (Cy) 300 mg/m2 and prednisone 40 mg/m2 both given orally from day 1 to day 5, followed by 6 CHOP courses every other 3 month in case of response. Fludarabine (25 mg/m2 /d IV for 5 consecutive days) was used in case of progression after 3 CHOP or non response after 6 CHOP. Conventional therapy was compared to high dose therapy with autologous CD34+ purified stem cell support (Arm B), using as consolidation of Complete Remission (CR) (NCI criteria) or Very Good Partial Response (VGPR, defined by >50 % tumoral response and < 30 % bone marrow lymphocyte count) obtained after 3 monthly courses of CHOP. In case of absence of CR or VGPR, 3 to 6 monthly-courses of fludarabine were realized before mobilization with Cy 4 g/m2 + G-CSF administration. Conditioning regimen included TBI 12 Gy and Cy 60 mg /kg /d for 2 days. Study end points included Event Free Survival (EFS), toxicity, feasibility. Between March 1999 and December 2004, 86 patients were randomized of which 79 were evaluable. A number of 38 patients were randomized to CHOP regimen and 41 to high dose therapy. The groups were well-balanced; 29% females, mean age 53 years (35 to 61), 67 % B and 25 % C Binet stages, 2 patients with A stage were included, 1 stage was not mentioned. In Arm B, 13 out of 41 patients were not transplanted because of disease progression (n=7), sepsis shock and death during the first CHOP course (n=1), patient’s refusal (n=1), graft contamination (n=1), mobilization failure (n=2) and violation criteria (n=1). CD34+ cells purification was performed in 69% of the grafts. Post transplant grade 3–4 non-hematological toxicity was mainly infectious (2 CMV and 1 aspergillus infections). Second cancers occurred in 3 patients in Arm A; skin cancer (n=1), breast cancer (n=1), Acute Myeloid Leukemia (AML) + skin cancer (n=1). One pretransplant case of skin cancer was reported in Arm B. Six patients died in Arm A from disease progression (n=5), AML (n=1) and 3 in Arm B from toxic death during the first course of CHOP (n=1), disease progression (n=2). As an intent-to-treat analysis and with a median follow-up time of 30 months (range 1–74), median EFS was 23.6 months in Arm A and 63.1 months in Arm B (p<0,001). In conclusion, front-line high dose therapy with autologous CD34+ purified stem cell support in B and C Binet stages B-CLL patients is feasible and has promising efficacy. Transplant-related toxicity appears to be acceptable. Longer follow-up as well as on-going VH mutational analysis will be necessary to precise the impact of autologous transplantation on overall survival in high-risk B-CLL.

High-Dose Bi-Weekly THP-COP Induction Treatment Followed by High-Dose Therapy with Autologous Peripheral Blood Stem Cell Transplantation for Advanced-Stage Follicular Lymphoma as First-Line Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5207-5207
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Masutaka Higashimura ◽  
Akihito Momoi ◽  
Nobuhiro Tsukada ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Advanced Stage ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: Most patients with advanced-stage follicular lymphoma(FL) cannot be cured by conventional chemotherapy and have median survival of 7 to 10 years. High-dose chemotherapy (HDT) supported by autologous stem cell transplantation(ASCT) gives a survival benefit for patients with aggressive lymphoma. Recent several multicenter studies have shown that clinical and molecular remissions can be attained in patients with FL receiving intensified high-dose sequential chemotherapy and autografting. We have reported the efficacy and safety of high-dose bi-weekly THP-COP with G-CSF support (HDBW-TCOPG) for non-Hodgkin’s lymphoma. Therefore, we performed a pilot clinical trial to evaluate the efficacy and toxicity of HDBW-TCOPG followed by HDT with ASCT as first-line therapy in patients with advanced-stage FL. Patients and methods: Between August 1998 and December 2003, 10 Japanese patients with previously untreated FL from whom informed consent was obtained were included in this single-center pilot study. Median age was 48 years. All patients had stage 3 or 4 disease, aaIPI LI 8 and HI 2. Histological subtypes of FL included grade 1 4; grade 2 4; grade 3a 2. HDBW-TCOPG consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 from day 1 to 5; lenograstim 2.0 mg/kg/day from day 3. Five patients who enrolled after rituximab was approved for indolent B-cell lymphoma in Japan received induction therapy combined HDBW-TCOPG with rituximab 375mg/m2 on day -2 (R-HDBW-TCOPG). Six cycles were administered at intervals of two weeks. PBSC were collected during the later cycles of HDBW-TCOPG or on the recovery of high-dose etoposide regimen (500mg/m2 for 3 days) administered after the completion of HDBW-TCOPG. Leukaphereses were performed until a minimum of 2.0x106/kg CD34+ cells had been collected. The conditioning regimen consisted of ranimustine 200mg/m2 on day-7 and -2; paraplatin 300mg/m2 on day -6, -5, -4, -3; etoposide 500mg/m2 on day −5, −4, −3; cytarabine 2.5 g/m2 every 12 hours on day −2, −1 (MCE-CA regimen) in 2 patients or cyclophosphamide 50mg/kg on day −2, −1 (MCEC regimen) in 8 patients. Results: Sufficient numbers of PBSC were collected in 5 of 7 patients mobilized with HDBW-TCOPG and in all 5 patients with high-dose etoposide. The median time to reach total number of leukocytes of 1.0 x109/l was nine days (range 8–11). All 10 patients who were in PR at the end of HDBW-TCOP(G) achieved CR post APBSCT. After a median follow up of 36.6 months (range 7–66 months) PFS and OS are 90% and 90%, respectively, for all patients. One patient developed secondary myeloid leukemia with t(3;21) and died at 35 months after APBSCT without signs of recurrence of lymphoma. Another patient who relapsed at 35 months after transplantation. IgH or BCL2 rearrangement was detected by PCR analysis prior to therapy in three patients and one of them still showed detectable disease after HDBW-TCOPG induction. However, all three patients demonstrated MRD negativity after HDT with ASCT. Conclusion: HDBW-TCOPG as induction therapy followed by HDT with ASCT is feasible for advanced-stage FL with acceptable toxicity, and this short term highly intensified therapy may induce cure of the disease by minimizing MRD, but longer follow up is needed to evaluate the impact on survival.

Nilotinib Versus High-Dose Imatinib in Early Chronic Phase CML Patients Who Have Suboptimal Molecular Responses to Standard-Dose Imatinib: Updated Data From RE-Nice Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3775-3775 ◽  
Author(s):  
Soo-Young Choi ◽  
Sung-Eun Lee ◽  
Soo-Hyun Kim ◽  
Eun-Jung Jang ◽  
Jin-hwa Lee ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Standard Dose ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
High Dose ◽  
Molecular Response ◽  
Long Term Outcomes ◽  
First Line

Abstract Abstract 3775 Background. In chronic myeloid leukemia (CML), achievement of optimal responses by time point has improved long-term outcomes. In contrast, several clinical studies investigating the clinical implications of suboptimal response showed that patients with suboptimal responses tend to have poor long-term outcomes. In IRIS study, patients who achieved major molecular response (MMR) at 18 months had event-free survival (EFS) benefit, compared to those who achieved complete cytogenetic response (CCyR) without MMR. However, the best treatment for these patients is still not confirmed. By the previous studies, sustaining standard-dose of imatinib (IM) is expected to yield less than 20 percent of additive MMR. In this prospective study, we investigated whether switching to nilotinib (NIL) or high-dose IM may be more effective for patients with suboptimal molecular response to IM as first-line therapy. Methods. Early chronic phase (CP) CML patients who have achieved CCyR but no MMR after at least 18 months and up to 24 months (≤ 18 to ≥24 months) on first-line IM therapy at a daily dose of 400 mg were enrolled in this clinical trial, and informed consents were obtained from all patients. In NIL arm, patients received oral dose of 400 mg BID (800 mg/day) and in high-dose IM arm, patients received 800 mg/day administrated as 400 mg BID. Primary endpoint is to evaluate the cumulative MMR rates by 12 months, and secondary endpoints are to evaluate the cumulative MMR, MR4.0 and undetectable molecular residual disease (UMRD) rates during further 24 month follow-up. Safety profiles will also be assessed. Patients showing lack of response (lack of complete hematologic response (CHR) at 6 months, increasing WBC, no major cytogenetic response (MCyR) at 24 months), loss of response (loss of CHR or MCyR) or severe intolerance to treatment were allowed to crossover to the alternative treatment. Results. With a data cut-off date of 10 Jul 2012, a total of 43 patients were randomized into NIL arm (n = 22) or high-dose IM arm (n = 21). With a median follow-up of 15 months (range, 1–36), all patients have maintained CCyR without progression to advanced disease, and progressive decrease in BCR-ABL1 transcript levels was observed in all patients. Cumulative incidence (CI) of MMR by 12 months showed no significant difference between NIL arm and high-dose IM arm (37.8 ± 11.9% vs 34.8 ± 10.6%, P = 0.789). In NIL arm, 3 in 22 (14%) and 2 in 22 (9%) patients achieved MR4.0 and UMRD, respectively, and in high-dose IM arm, 1 in 21 (5%) patients achieved MR4.0. Overall, the patients treated with high-dose IM showed toxicities more frequently, such as fatigue, dyspnea and decreased phosphate. In addition, 10 patients in high-dose IM arm have cross-over to NIL treatment due to lack of response (n=9) and intolerance (n=1), and the median duration of NIL treatment was 14 months (range, 7–26 months). Among them, 5 (50%) patients have achieved MMR with a median NIL treatment duration of 12 months (range, 3–18). Conclusions. These results demonstrate that early switching to NIL or dose escalation of IM could be recommended, considering the results of standard dose of IM in suboptimal molecular responders. When the tolerability of treatment was considered for switching to NIL or high-dose IM, NIL may be preferred. Through further clinical investigation on a large patient population and longer period observation, the efficacy and safety of early intervention of suboptimal molecular response using NIL or dose escalation of IM will be needed. Updated data with longer follow-up duration will be presented in the meeting. Disclosures: No relevant conflicts of interest to declare.

First-LINE Treatment With High-Dose Dexamethasone Terapy For Adult Primary Inmune Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1081-1081
Author(s):  
Dana Diaz-Canales ◽  
Maria Rosario Prieto-Bonilla ◽  
Maria Eva Mingot-Castellano ◽  
Ana Isabel Heiniger Mazo
Keyword(s):  
High Risk ◽  
Median Time ◽  
High Dose ◽  
Similar Response ◽  
Line Treatment ◽  
First Line ◽  
High Dose Dexamethasone ◽  
Number Of Patients ◽  
First Line Treatment

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder with a very variable outcome. Bleeding manifestations and platelets count are considered the main criteria to start treatment in these patients. The initial recommended therapy are corticosteroids and intravenous immunoglobulin (IgsIV). The aim of our study is the description of efficacy and safety of high-dose dexamethasone (Dx) used as frontline therapy in newly diagnosed ITP patients. Methods A series of patients diagnosed in our centre from March 2009 to August 2012 has been studied. They have received first-line treatment with Dx (40 mg/d four consecutive days every 2 or 4 weeks) for 1 to 6 courses. Sex, age, cardiovascular risk factors, reasons to treat, response, courses of treatment, complications and relapse rate were recorded and analyzed. Results Our series of twenty-nine patients, 18 women (62%) and 11 men (38%), had a median age of 54 years (range 16-92 years). Twenty-five patients (86%) were treated after low platelet counts (30x 10e9 / L) with or without clinical bleeding, whereas the other four patients were treated as a surgery preparation. One patient received a reduced dose of Dx (20 mg/d x 4 days) because of comorbidities and high risk of infection. In thirteen patients, IgsIV were added to Dx in the first course (1g/kg/d x 2 days), because of high bleeding risk or more severe bleeding at diagnosis. Platelets count at baseline was 15x109/ L (range 1-29 x109/ L). Ninety-three percent of patients responded after the first course of Dx (69% complete response CR, 24% partial response PR), and 45% of the patients did not require additional Dx treatment. The median time to reach a response was 5 days since the first day of treatment (range 2-60). The sixteen patients who need more than one course received a median of 4 (range 2-10), all of them without IgsIV. After a median follow-up of 14 months (range 2-45), 69% of these patients maintained the response without further treatment. Therefore, the overall response of the series reaches 83%. After 6 courses of treatment, 5 subjects did not achieved response and were classify as corticosteroid dependent. Of these, one patient was splenectomized and at present he remains at CR after 30 months of follow up. Another patient is waiting for splenectomy, and other three received thrombopoietin analogs, remaining all them in CR under treatment. Thirteen patients received a combination of Igs and Dx in the first course due to high risk of bleeding (platelets less than 20 x 10e9/L and hemorrhagic manifestations). Eleven of them (81%) achieved response (4 PR, 7CR) at a median time of 4 days (range 2–60). After the first course of treatment, 61% (8 of 13) of patients receiving both IgsIV and Dx responded, vs 35% (5 of 16) of those treated only with Dx. This difference was not statistically significant, probably because of the small number of patients in our series. All patients treated with IgsIV and Dx in the first course got the best response after 4 cycles of dexamethasone, compared to 75% of subjects treated with Dx for 4 to 6 courses. Dx was usually well tolerated, since only 13% of the patients experienced side effects: one case of hypertension, another patient developed hyperglycemia associated to corticosteroids and other two presented mild transient steroid psychosis episodes. Infectious events were not observed. Conclusions Treatment with high-dose dexamethasone as first-line treatment for ITP is a good alternative to prednisone because it shows a high efficacy and a good safety profile. In our experience, the association of IgsIV and Dx in the first course may improve the response rate and decrease the total dose of steroids needed to achieve a similar response. Disclosures: No relevant conflicts of interest to declare.

Eltrombopag and High-Dose Dexamethasone As First Line Treatment For ITP

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3544-3544
Author(s):  
David Gomez-Almaguer ◽  
Miguel Angel Herrera-Rojas ◽  
Andres Gomez-de Leon ◽  
Olga Graciela Cantú-Rodríguez ◽  
Cesar H Gutiérrez-Aguirre ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Line Treatment ◽  
Front Line ◽  
First Line ◽  
High Dose Dexamethasone ◽  
Line Therapy ◽  
First Line Treatment

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that involves antibody and cell mediated destruction of platelets as well as suppression of their production. Prednisone is the initial standard therapy in adults1. High-dose dexamethasone as front-line therapy given as pulses of 40 mg per day for 4 consecutive days, was effective in 85% of patients, nevertheless, 50% relapsed within six months2. The prices of ITP drugs for 1 month of treatment in an adult range from prednisone; $16, eltrombopag; $5,934, intravenous immune globulin (IVIG) (80 g); $9,648, to rituximab (2 g); $15,5963. Only prednisone/dexamethasone and eltrombopag are available in oral presentation, for this reason, ambulatory treatment is an alternative for these patients. The trombopoietin receptor agonists are effective for the treatment of patients with chronic ITP, although response is dependent on continued administration. Eltrombopag is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of thrombopoietin. This drug effectively raises the platelet count in adult patients (aged 18 years and over) as second/third line therapy, that is for patients refractory to corticosteroids and IVIG who have had their spleen removed or when splenectomy is not an option4. Our group, as well as others, has previously sought to improve response rates in these patients, particularly with the use of rituximab5, 6. To our knowledge neither eltrombopag nor romiplostim have been used as front line therapy in ITP, therefore the purpose of this study was to assess the efficacy of eltrombopag and dexamethasone in this setting. Patients and Methods This was a prospective, phase 2 study, using the combination of eltrombopag (50 mg PO once a day for 4 weeks) and high-dose dexamethasone (40 mg PO days 1,2,3,4) in untreated adult patients with immune thrombocytopenia or in patients with less than 7 days of treatment with corticosteroids. Complete response (CR) was defined as an increase in platelet count >100×109/L. Partial response (PR) was defined as an increase in the platelet count greater to 30 ×109/L according to standard criteria. Duration of response was considered from the day of initial administration to the first time of relapse (platelet count <30×109/L). Results Twelve consecutive patients were enrolled from June 2012 to June 2013, 6 women and 6 men. The median age at diagnosis was 50 years (range, 20 - 80 years). The median platelet count at diagnosis was 7 x 109/L (range, 2 - 29 x 109/L). Patients were followed for a median of 2.5 months (range 1.1 - 13). After steroid treatment at day +5, ten patients had responded (83.3%), five had achieved CR (41.7%), and five PR. After completing treatment with eltrombopag at day +34, all patients responded (100%), nine patients achieved CR (75%) and three PR (25%). Two patients relapsed in a median time of 39.5 days (range, 30.1 - 49), both regaining CR after treatment with another high-dose dexamethasone course and low-dose rituximab (4 doses of 100 mg every week). At 3 months follow-up 66.7% remained in CR and 33.3% in PR (n=6). At 6 months follow-up two patients remained in CR and two in PR (n=4). Time to best response achieved was 34 days from diagnosis (range, 19 – 64.1). At the end of follow-up 9 patients (75%) remained in CR and 3 patients in PR (25%). Total treatment cost per patient was $1,640 approximately. Conclusion Currently the initial treatment of ITP patients is based on prednisone or high dose dexamethasone with or without IVIG. This approach is associated with high cost and high relapse rate. The results from our pilot study suggest that high dose dexamethasone and eltrombopag are very effective as first line treatment for acute ITP in adults. This treatment is ambulatory, affordable and well tolerated; however, we still don't know if this approach will have a favorable impact on the relapse rate of this disease. Disclosures: Off Label Use: Eltrombopag as first line treatment for ITP.

Outcomes in patients (pts) with advanced renal cell carcinoma (aRCC) who discontinued (DC) first-line nivolumab + ipilimumab (N+I) or sunitinib (S) due to treatment-related adverse events (TRAEs) in CheckMate 214.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 581-581 ◽  
Author(s):  
Nizar M. Tannir ◽  
Robert J. Motzer ◽  
Elizabeth R. Plimack ◽  
David F. McDermott ◽  
Philippe Barthelemy ◽  
...  
Keyword(s):  
Risk Groups ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Post Hoc ◽  
Study Dose ◽  
Clinical Trial Information

581 Background: The phase 3 CheckMate 214 trial demonstrated superior efficacy for N+I vs S in aRCC, although more patients discontinued N+I compared with S due to TRAEs. This is a post hoc analysis of outcomes in pts who DC N+I or S due to TRAEs. Methods: Untreated pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3Wx4 (induction) and then N 3 mg/kg Q3W (maintenance), or S 50 mg daily for 4 wk on, 2 wk off (6-wk cycles). This analysis includes all pts who DC due to TRAEs reported during extended follow-up (≤100 d after last study dose). Results: Of 550 N+I randomized pts, 135 (25%) DC due to TRAEs, most commonly increased ALT, diarrhea, and increased AST (all 3%); 64 (12%) of 535 S randomized pts DC due to TRAEs, most commonly increased ALT, diarrhea, and pancreatitis (all 1%). In N+I pts who DC due to TRAEs, 47% DC during N+I induction, 7% completed induction but no N maintenance, and 46% completed induction and received N maintenance (median [range] 8 [1–47] doses). At 30-mo minimum follow-up, ORR per investigator, CR rate, and 24-mo OS rate were higher in pts who DC N+I vs S due to TRAEs. Outcomes in pts who DC S due to TRAEs were similar to those in all S ITT pts and worse than in N+I pts who DC due to TRAEs (Table). At 24 mo, 42% of pts who DC N+I due to TRAEs were alive and free from second-line therapy. Consistent outcomes were seen in pts who DC N+I due to TRAEs across IMDC risk groups (data to be presented). Pts who DC N+I due to TRAEs experienced more immune-related select TRAEs and received more high-dose steroids (≥40 mg prednisone daily or equiv.), but times to onset and resolution and resolution rates of select TRAEs were similar vs all treated N+I pts. Conclusions: Discontinuation of first-line N+I due to TRAEs did not result in impaired outcomes, and a high proportion of pts remain alive and free from second-line therapy. Clinical trial information: NCT02231749. [Table: see text]

scholarly journals Incidence and Outcomes of Post-Transplant Lymphoproliferative Disease after 5365 Solid Organ Transplants over a 20 Year Period at 2 UK Transplant Centres

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 888-888
Author(s):  
Anna Santarsieri ◽  
Andrew Butler ◽  
William Gelson ◽  
Stephen Pettit ◽  
John F Rudge ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Lymphoproliferative Disease ◽  
First Year ◽  
Solid Organ ◽  
Line Treatment ◽  
First Line ◽  
Post Transplant

Abstract Background: Post-transplant lymphoproliferative disease (PTLD) confers a high morbidity and mortality in a vulnerable population. We present the epidemiology and outcomes of PTLD in a large UK cohort of solid organ transplant (SOT) recipients who were transplanted over a 20-year period. Methods: This is a retrospective study of 5365 SOT recipients who had their first transplant between 2000 and 2021 at two UK transplant centres (Addenbrooke's Hospital and Papworth Hospital). We reviewed the records of all patients and found 142 who subsequently developed PTLD. For each type of transplant, we calculated the incidence rate of PTLD and cumulative incidence using a competing risk of death model. Survival was compared with the age-adjusted life expectancy of the UK population using the National life tables and a landmark analysis was performed to compare overall survival (OS) of PTLD patients from the date of diagnosis with the background survival of the transplant population. To compare treatment outcomes, a subset of 90 cases of monomorphic PTLD, DLBCL subtype were identified. 66 were treated with first-line Rituximab monotherapy and 24 received first-line R-Chemotherapy. Demographics, treatment response, and survival data were analysed with univariate and multivariate analysis to identify covariates associated with death in the first year post diagnosis of PTLD. Results: With a median follow-up time of 5.3 years, 142 of 5365 solid organ transplant recipients have developed PTLD (56/1965 kidney, 22/1428 liver, 12/327 simultaneous kidney-pancreas (SPK), 21/113 multivisceral (MVT), 10/778 heart, 15/503 bilateral lung, 3/148 single lung and 3/85 heart and lung). The incidence rate of PTLD was highest in the first year post-transplant in lung and MVT recipients. Cumulative incidence (shown in Figure 1) was 18% at 5 years post-MVT and 1-3% at 5 years following the other SOT types. Cumulative incidence was lowest for liver and heart transplants and was 10% at 20 years post-kidney transplantation. Median OS following SOT was 16 years which is significantly reduced compared with the age-adjusted UK population. There is a relatively high early mortality rate following diagnosis of PTLD and only patients surviving two years post diagnosis regained a similar longer-term survival to the non-PTLD SOT cohort. Treatment with rituximab monotherapy (RM) is now a standard of care for monomorphic PTLD 1. Outcomes for monomorphic patients were compared between those treated with RM (n=66, median follow-up 2.2 y) and R-Chemotherapy (n=24, median follow-up 5.2 y). The two groups were well matched for age and IPI. Of the 66 RM patients, 22 (33%) achieved complete remission with RM and required no further treatment. A further 18 (27%) patients achieved remission following further treatment with chemotherapy/surgery/CTL. 6/66 (9%) patients died of progressive disease (PD), 9/66 (14%) died pre-remission of non-PTLD causes and 11/66 (17%) died in remission of unrelated causes. In the R-Chemotherapy group, 22 patients received R-CHOP and 2 received R-CVP (n=24). 8 (33%) patients are alive and in remission after first line treatment and a further 3 patients (13%) after second line treatment. 2/24 (8%) patients died of PD, 4/24 (17%) died pre-remission of non-PTLD causes and 7/24 (30%) died post-remission of unrelated causes. There is no significant difference in OS between the two groups. Only a minority of deaths were due to PD and death from non-lymphoma causes pre and post remission remain considerably higher than non-PTLD SOT patients up to 2 years post treatment (Figure 1). Multivariate analysis of all 90 monomorphic PTLD patients identified IPI3+ as the strongest pre-treatment variable associating with inferior 1 year OS. Interestingly IPI3+ did not retain this significance when R-chemo patients were analysed alone. Conclusion: With this large SOT dataset we have mapped the cumulative incidence of PTLD over a 20 year period and highlight transplanted organ-specific differences in PTLD incidence over time. Treating monomorphic DLBL patients first-line with RM rather than R-chemotherapy does not appear to compromise OS, but the number of patients dying from non-lymphoma causes pre- and post-treatment remains high with both treatment approaches, with poor OS compared with age-matched non-PTLD SOT recipients. 1Trappe et al. Lancet Oncol; 2012 13(2):196-206 Figure 1 Figure 1. Disclosures Santarsieri: Janssen: Honoraria. Uttenthal: Roche: Other; Takeda: Other; Jazz: Other. Follows: Janssen, Abvie, Roche, AZ: Other.

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