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757 citation(s) found for "Saénz, Ricardo".

Insulinoma: A Recurrent Pancreatic Tumor Amendable to Computed Tomography–Guided Ethanol-Lipiodol Injection
Alnahhal, Khaled I. , Ghoz, Hassan , Paz‐Fumagalli, Ricardo , Lukens, Frank , Zaver, Himesh B. , Paz-Fumagalli, Ricardo, Raimondo, Massimo , Lukens, Frank J.

ACG Case Reports Journal | February 27, 2021 | Volume: 8 | Issue: 2 | Pages: e00539

10.14309/crj.0000000000000539 | PMID 33654702 Get It

ABSTRACT Insulinomas are rare, with an annual incidence of 1–4 people per mission. Insulinomas are the most common functioning endocrine neoplams of the pancreas. Endoscopic ultrasound has both diagnostic and therapeutic yield in undifferentiated pancreatic tumors. We present a case of a recurrent insulinoma, refractory to surgical and medical management diagnosed with endoscopic ultrasound. Our case uniquely conveys a successful, alternative approach to addressing symptomatic insulinomas refractory to surgical or medical management through computed tomography–guided percutaneous ethanol-lipiodol injection.
Cervical Chordomas: Multicenter Case Series and Meta-analysis
Akinduro, Oluwaseun O. , Vivas-Buitrago, Tito , Bydon, Mohamad , Gokaslan, Ziya L., Kalani, Maziyar A. , Quiñones‐Hinojosa, Alfredo , Moniz‐Garcia, Diogo , Domingo, Ricardo A. , Sousa‐Pinto, Bernardo , Clarke, Michelle J. , Abode-Iyamah, Kingsley

No container title available | February 24, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-229633/v1 Get It

Abstract Background En bloc spondylectomy is the gold standard for surgical resection of sacral chordomas (CHO), but the effect of extent of resection on recurrence and survival in patients with CHO of the cervical spine remains elusive. Methods MEDLINE, Embase, Scopus, and Cochrane were systematically reviewed. Patients with cervical CHO treated at three tertiary-care academic institutions were reviewed for inclusion. We performed an individual participant data meta-analysis to assess the overall survival (OS) and progression free survival (PFS) after en bloc-gross total resection (GTR) and intralesional-GTR compared to subtotal resection (STR). We then performed an intention-to-treat analysis including all patients with attempted en bloc resection in the en bloc group, regardless of the surgical margins. Results There was a total of 13 series including 161 patients with cervical CHO, including our current series of 22 patients. GTR (en bloc-GTR + intralesional-GTR) was associated with a significant decrease in the risk of local progression (pooled hazard ratio (PHR) = 0.22; 95% CI = 0.08–0.59; p = 0.003) and risk of death (PHR = 0.31; 95%; CI:0.12–0.83; p = 0.020). A meta-regression analyses determined that intralesional-GTR improved PFS (PHR = 0.35; 95%CI = 0.16–0.76; p = 0.009) as well as OS (PHR = 0.25; 95%CI = 0.08–0.79; p = 0.019) when compared to STR. En bloc-GTR was associated with a significant reduction in the risk of local progression (PHR = 0.06; 95%CI = 0.01–0.77; p = 0.030), but not a decreased OS (PHR = 0.50; 95% CI = 0.19–1.27; p = 0.145). Our intention-to-treat analyses revealed a near significant improvement in OS for the en bloc group (PHR: 0.15; 95%CI:0.02–1.22; p = 0.054), and nearly identical improvement in PFS. Radiation data was not available for the studies included in the meta-analysis. Conclusion This is the first and only meta-analysis of patients with cervical CHO. We found that both en bloc-GTR and intralesional-GTR resulted in improved local tumor control when compared to STR.
Aspiration Thrombectomy: 2-Dimensional Operative Video
Turner, Raymond D , Turk, Aquilla S , Bain, Mark, Bendock, Bernard, Binning, Mandy J., Boulos, Alan S. , Crowley, Webster, Fessler, Richard D., Guterman, Lee R., Hoit, Daniel , Hopkins, L. Nelson , Howington, Jay U., James, Robert F. , Jankowitz, Brian T. , Kan, Peter , Khalessi, Alex A, Kim, Louis J. , Langer, David J. , Lanzino, Giuseppe, Levitt, Michael , Levy, Elad, Mack, William J. , Mericle, Robert A., Ogilvy, Chris, Replogle, Robert, Riina, Howard A. , Saugaveau, Eric, Schirmer, Clemens M. , Spiotta, Alex, Sultan, Ali, Veznedaroglu, Erol, Welch, Babu G. , White, Jonathan, Schirmer, Clemens M , Chaudry, Imran , Vargas, Jan , Arthur, Adam Stephen , Grande, Andrew Walker , Hanel, Ricardó A. , Kim, Louis J. , Lanzino, Giuseppe , Levitt, Michael, Levy, E, Lopes, Demetrius K. , Mocco, J , Pandey, Aditya S , Ringer, Andrew J. , Rodriguez, Rafael, Siddiqui, Adnan H. , Tawk, Rabih G. , Thomas, Ajith J , White, Jonathan A.

Operative Neurosurgery | February 12, 2021 | Volume: 20 | Issue: 4 | Pages: E286-E287

10.1093/ons/opaa471 | PMID 33575807 Get It

Abstract Acute ischemic stroke is one of the leading causes of disability and mortality worldwide. There have been significant improvements to the treatment of acute ischemic stroke over the past 5 yr, specifically related to strokes caused by large vessel occlusions. Stent retrievers with and without local aspiration and direct aspiration alone have all been demonstrated as viable treatment options for this patient population. This case represents the surgical technique for direct aspiration for the treatment of large vessel occlusion. A 76-yr-old man presented with right-sided weakness and aphasia. His last known normal was 5 h ago. His NIHSS (National Institutes of Health Stroke Scale) was 18. The noncontrast computed tomography (CT) did not show a significant infarct burden and ASPECTS (Alberta Stroke Program Early CT Score) of 9. CT angiogram demonstrated a left M1 occlusion. The patient was not a candidate for tissue plasminogen activator (tPA) because of time to presentation; however, the patient was deemed to be a candidate for emergent thrombectomy. Consent was obtained per institutional guidelines for the emergent procedure and the video recording. The video demonstrates a direct aspiration thrombectomy technique for the treatment of stroke. The patient successfully underwent direct aspiration thrombectomy with a TICI 3 (thrombolysis in cerebral infarction) recanalization.
Management of Thromboembolic Complications During Aneurysm Coiling: 2-Dimensional Operative Video
Domingo, Ricardo A. , Santos, Jaime L. Martínez , Ravindran, Krishnan , Tawk, Rabih G. , Bain, Mark, Bendock, Bernard, Binning, Mandy J., Boulos, Alan S. , Crowley, Webster, Fessler, Richard D., Guterman, Lee R., Hoit, Daniel , Hopkins, L. Nelson , Howington, Jay U., James, Robert F. , Jankowitz, Brian T. , Kan, Peter , Khalessi, Alex A, Kim, Louis J. , Langer, David J. , Levitt, Michael R. , Mack, William J. , Mericle, Robert A., Ogilvy, Chris, Replogle, Robert, Riina, Howard A. , Ringer, Andrew J. , Saugaveau, Eric, Schirmer, Clemens M. , Spiotta, Alex, Sultan, Ali, Turner, Raymond D , Veznedaroglu, Erol, Welch, Babu G. , White, Jonathan A. , Ogilvy, Christopher S. , Martinez Santos, Jaime L, Tawk, Rabih G , Levitt, Michael R , Schirmer, Clemens M , Domingo, Ricardo A , Ogilvy, Christopher S , Arthur, Adam Stephen , Grande, Andrew Walker , Hanel, Ricardó A. , Kim, Louis J. , Lanzino, Giuseppe , Levy, Elad I. , Lopes, Demetrius K. , Mocco, J , Pandey, Aditya S , Rodriguez, Rafael, Siddiqui, Adnan H. , Thomas, Ajith J

Operative Neurosurgery | February 12, 2021 | Volume: 20 | Issue: 5 | Pages: E348-E349

10.1093/ons/opaa480 | PMID 33571364 Get It

Abstract Thromboembolic complications during aneurysm coiling are rare, with higher rates noted in ruptured aneurysms as patients are not usually premedicated with dual antiplatelet therapy. 1,2 Management includes a series of escalating strategies, including medical therapy and intra-arterial thrombolysis. 3-6 Additional strategies include mechanical thrombectomy with suction aspiration and stent retrievers. 3 Intracranial stenting can be used as a last resource, especially in ruptured cases given the need for dual antiplatelets to prevent stent thrombosis. 2 We present the case of a 42-yr-old man with a ruptured left internal carotid artery aneurysm with associated intracranial and intraventricular hemorrhage. The patient was initially presented to an outside facility after he was found in bed unable to speak and with right hemiparesis. The patient consented for surgery and underwent external ventricular drain (EVD) placement for the treatment of obstructive hydrocephalus, followed by diagnostic cerebral angiogram and aneurysm coiling. After the deployment of the last coil, control angiogram showed a small filling defect at the interface between the aneurysm neck and the distal vessel. The patient received intravenous heparin for therapeutic ACT and aspirin load. After progressive enlargement of the thrombus, the patient received intra-arterial glycoprotein (GP) IIB/IIIA inhibitors with a microcatheter positioned proximal to the thrombus. As the thrombus mass continued to enlarge, mechanical thrombectomy with an aspiration catheter was performed twice. Follow-up angiogram 20 min after the second aspiration demonstrated near-complete resolution of the thrombus. The patient recovered from his right hemiparesis, and he was discharged to rehabilitation on POD #21.
The Role of Angioplasty Alone in Intracranial Atherosclerosis: 2-Dimensional Operative Video
Cohen-Cohen, Salomón , Brinjikji, Waleed , Bain, Mark, Bendock, Bernard, Binning, Mandy J., Boulos, Alan S. , Crowley, Webster, Fessler, Richard D., Guterman, Lee R., Hoit, Daniel , Hopkins, L. Nelson , Howington, Jay U., James, Robert F. , Jankowitz, Brian T. , Kan, Peter , Khalessi, Alex A, Kim, Louis J. , Langer, David J. , Levy, Elad, Mack, William J. , Mericle, Robert A., Ogilvy, Chris, Replogle, Robert, Riina, Howard A. , Saugaveau, Eric, Schirmer, Clemens M. , Spiotta, Alex, Sultan, Ali, Turner, Raymond D , Veznedaroglu, Erol, Welch, Babu G. , Schirmer, Clemens M , Lanzino, Giuseppe , Arthur, Adam Stephen , Grande, Andrew Walker , Hanel, Ricardó A. , Kim, Louis J. , Levitt, Michael R. , Levy, E, Lopes, Demetrius K. , Mocco, J , Pandey, Aditya S , Ringer, Andrew J. , Rodriguez, Rafael, Siddiqui, Adnan H. , Tawk, Rabih G. , Thomas, Ajith J , White, Jonathan Samuel

Operative Neurosurgery | February 12, 2021 | Volume: 20 | Issue: 5 | Pages: E350-E351

10.1093/ons/opaa479 | PMID 33571354 Get It

Abstract Intracranial atherosclerosis disease (IAD) is the cause of stroke in up to 10% of cases. Symptomatic IAD results mainly from hypoperfusion, embolic phenomenon, and occlusion. Treatment consists of conservative management with aggressive medical treatment, surgery, and endovascular therapy. 1,2 This video is about a 62-yr-old male who presented with left-sided hemiparesis and right gaze preference secondary to an acute ischemic stroke in the right middle cerebral artery (MCA) territory treated initially with tissue plasminogen activator (tPA). Head computed tomography (CT) angiography (CTA) revealed occlusion of the extracranial and cavernous segments of the internal carotid artery (ICA). CT perfusion (CTP) showed hypoperfusion in the MCA territory and magnetic resonance imaging (MRI) revealed multifocal, wedge-shaped areas of restricted diffusion in the right hemisphere. During his hospitalization, he experienced worsening of his symptoms in the setting of hypoperfusion (hypotension). The patient underwent a cerebral angiogram with thrombectomy and submaximal angioplasty (SA). Successful revascularization of the right ICA was obtained. No procedure-related complications occurred, and the patient's neurological exam improved. SA can be as efficient and a safer option than conventional angioplasty or angioplasty and stenting for symptomatic IAD. The patient consented for the procedure and for the video production.
Type IV Collagen Immunostaining Is a Simple, Reliable Diagnostic Tool for Distinguishing Between Adenomatous and Normal Pituitary Glands
Lloyd, Ricardo V., McKeever, Paul E. , Jarzembowski, Jason A.

Archives of Pathology & Laboratory Medicine | February 11, 2021 | Volume: 131 | Issue: 6 | Pages: 931-935

10.5858/2007-131-931-ticiia | PMID 17550321 Get It

Abstract Context. —Pituitary adenomas are clinically diagnosed based on radiologic studies and/or secondary effects of hormone production. Definitive pathologic identification relies on immunohistochemical detection of a clonal population of hormone-producing cells. However, not all adenomas secrete hormones, so performing a battery of stains is inefficient. Reports have shown decreased type IV collagen in the stroma of other epithelial tumors. Objective. —To validate type IV collagen immunohistochemistry as a diagnostic method. Design. —We immunostained 27 adenomas and 19 normal pituitaries. The areas with the sparsest type IV collagen fibers were viewed at 3 magnifications (×10, ×20, and ×40 objectives), counting 1, 3, or 10 microscopic fields. A field was scored as “traversable” if a path existed from any point on the periphery of the field to a point on the approximately opposite periphery that did not cross any stained fibers. Results were compared with reticulin staining and to the existing diagnosis previously determined by histology, hormone immunostaining, and clinical correlation. Results. —Adenomas have less type IV collagen in their basement membranes, leading to sparser, trabecular staining in neoplasms versus a more rigid meshwork pattern in normal glands. One might envision the stained fibers as maze walls—one can traverse medium-powered fields in an adenoma, but one hits dead ends and gets trapped in those of a normal gland. Finding a single representative ×10 field to be traversable was 97.5% sensitive and 96.5% specific for an adenoma. Reticulin staining yielded identical results. Conclusions. —Type IV collagen immunostaining is a simple and reliable method of diagnosing pituitary adenomas.
Perineurioma: A Distinctive and Underrecognized Peripheral Nerve Sheath Neoplasm
Ellinger, Fred, Oliveira, André M. , Macarenco, Ricardo

Archives of Pathology & Laboratory Medicine | February 11, 2021 | Volume: 131 | Issue: 4 | Pages: 625-636

10.5858/2007-131-625-padaup | PMID 17425397 Get It

Abstract Context. —Perineuriomas are benign peripheral nerve sheath neoplasms composed of perineurial cells with characteristic immunohistochemical and ultrastructural features. They have been traditionally classified into two main types according to their location—intraneural and extraneural—and overlap histologically with many other tumors, which may be diagnostically challenging to general surgical pathologists. Objective. —To review the clinical, morphologic, immunohistochemical, ultrastructural, cytogenetic, and molecular genetic aspects of perineurioma, as well as to discuss its clinicopathologic variants and differential diagnosis. Data Sources. —English-language literature published between 1966 and 2005 was reviewed. Conclusions. —The correct identification of perineuriomas is important to avoid unnecessary overtreatment. The histologic diagnosis should be confirmed through immunohistochemical studies (including epithelial membrane antigen, S100 protein, and more recently described antibodies such as claudin-1 and GLUT1) or electron microscopy. Cytogenetic and molecular genetic studies are still of limited value for the diagnosis of perineuriomas but may play a fundamental role in excluding important differential diagnoses and also in helping elucidate the biology of these poorly known neoplasms.
Variation in the Treatment of Multiple Myeloma in the Real World
Chhun, Leena, Zheng, Cheng , Piboonvaranggoon, Jayne, Mallick, Elora, Wren, Jennifer, Nam, Grace, Barquilla, Ricardo Lopez, Dardac, Alexandra, Blau, Sibel , Senecal, Francis M. , Namburi, Swathi, Cowan, Andrew J. , Bensinger, William, Kumar, Shaji , Richardson, Paul G. , Blau, C. Anthony , Richter, Joshua , Richardson, Paul Gerard Guy , Anderson, Kenneth C.

Blood | February 8, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 43-44

10.1182/blood-2020-138705 Get It

Background: Here we describe an online network of patients with cancer, clinicians and researchers, layered on top of a comprehensive real world database of treatments and outcomes, continuously updated in near real time, and initially focused on multiple myeloma. Methods: Patients with multiple myeloma register at www.all4cure.com and sign HIPAA release forms to provide access to all of their medical records from all of the institutions from which they have received care. From the medical records, a structured dataset of treatments and lab results is extracted by a myeloma-dedicated team for display on each patient's de-identified, personalized dashboard. A discussion panel allows more than 1200 participating patients, clinicians and researchers to post comments or questions regarding each patient's specific circumstances. For each patient, lines of therapy and responses are determined according to IMWG and published criteria (Blood [2015] 126: 921-922). Here we report initial results from the treatments and responses among patients with multiple myeloma and plasma cell leukemia. Results: A total of 493 patients includes 26 with monoclonal gammopathy of undetermined significance (MGUS), 51 with smoldering myeloma, 408 with multiple myeloma, and 8 with primary plasma cell leukemia. Among patients with multiple myeloma, 42 (10.3%) had antecedent MGUS and/or smoldering myeloma. The average age is 65.6 (+/- 9.7). 50.9% are male and 49.1% are female. 42 states in the U.S. and 8 other countries are represented. Two patients with multiple myeloma had not started treatment by the time of this report. The remaining 414 patients with multiple myeloma or plasma cell leukemia received 1 to 16 lines of therapy. Among the 414 patients that received at least one line of therapy, a remarkable 89 distinct first line therapies were administered. The most common first line therapies were lenalidomide, bortezomib, dexamethasone (n=92), cyclophosphamide, bortezomib, dexamethasone (n=50), lenalidomide, bortezomib, dexamethasone + autologous stem cell transplant + lenalidomide maintenance (n=41), lenalidomide and dexamethasone (n=29), and bortezomib and dexamethasone (n=22). 62 patients received a first line therapy that was not received by any other patient in our database. This variation was attributable to participation in clinical trials, variation in the availability of drugs over time and different geographic locations, and the very large number of distinct combinations associated with multi-agent regimens. Seventy six percent of patients with multiple myeloma or plasma cell leukemia received a second line of therapy, 52% received a third line of therapy, 34% received a fourth line of therapy, 23% received a fifth line of therapy, and 18% received a sixth line of therapy. We observed a trend toward a decline in favorable responses with successive lines of therapy (Table 1) consistent with previous reports, with a correlation coefficient between the line of therapy and overall response rate of -0.74. Among the 76 patients who received 6 or more lines of therapy (247 lines of therapy in total), only 7 achieved stringent complete responses (sCRs), of which 5 were associated with a CAR-T therapy. Table 1 also shows a trend toward more rapid changes in treatment associated with later lines of therapy. 57 of 493 patients (12%) are deceased. Conclusions: Our findings reveal remarkable variation in the treatment of myeloma and provide a potentially valuable resource of up to date and current clinical features, prognosis, treatments, side effects, and outcomes of patients with myeloma in the real world. Table 1. Summary of lines of therapy and outcomes across 414 patients with multiple myeloma and plasma cell leukemia. The percentages of patients achieving sCR, ≥ PR (overall response rate - ORR), and ≥MR (clinical benefit rate - CBR) are shown for each line of therapy. Also depicted is the interval mortality and the mean and median number of days between the beginning of a line therapy and the beginning of the next line of therapy. Table Disclosures Richter: Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Sanofi: Consultancy; X4 pharmaceuticals: Consultancy; Oncopeptides: Consultancy; Adaptive biotechnologies: Consultancy; Secura bio: Consultancy; Astra Zeneca: Consultancy; BMS: Consultancy; Karyopharm: Consultancy; Antengene: Consultancy. Chhun:All4Cure: Current Employment. Zheng:All4Cure: Current Employment. Piboonvaranggoon:All4Cure: Current Employment. Mallick:All4Cure: Current Employment. Wren:All4Cure: Current Employment. Nam:All4Cure: Current Employment. Lopez Barquilla:All4Cure: Current equity holder in private company. Blau:All4Cure: Current equity holder in private company. Cowan:Janssen: Consultancy, Research Funding; Abbvie: Research Funding; Cellectar: Consultancy; Sanofi: Consultancy; Bristol Myers Squibb: Research Funding. Bensinger:BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Regeneron: Consultancy, Honoraria, Research Funding, Speakers Bureau. Kumar:Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Genecentrix: Consultancy; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Novartis: Research Funding; Merck: Consultancy, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Carsgen: Other, Research Funding; Dr. Reddy's Laboratories: Honoraria; Adaptive Biotechnologies: Consultancy; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; MedImmune: Research Funding; Tenebio: Other, Research Funding; BMS: Consultancy, Research Funding; Karyopharm: Consultancy; Cellectar: Other; Sanofi: Research Funding; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Kite Pharma: Consultancy, Research Funding. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Anderson:Oncopep and C4 Therapeutics.: Other: Scientific Founder of Oncopep and C4 Therapeutics.; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees. Blau:All4Cure: Current Employment, Current equity holder in private company.
Daratumumab Plus Lenalidomide and Dexamethasone (DRd) Compared to Daratumumab Plus Pomalidomide and Dexamethasone (DPd) in Relapsed Lenalidomide-Exposed or Refractory Multiple Myeloma (MM) Patients: The Mayo Clinic Experience
Abdulazeez, Mays F , Sher, Taimur , Alegria, Victoria R., Warsame, Rahma , Larsen, Jeremy T. , Kourelis, Taxiarchis , Kapoor, Prashant , Hayman, Suzanne R. , Reeder, Craig B. , Agrawal, Arshi, Chanan‐Khan, Asher , Moustafa, Muhamad Alhaj , Parrondo, Ricardo D , Roy, Vivek , Gonsalves, Wilson I. , Fonseca, Rafaël , Buadi, Francis K. , Dingli, David , Ailawadhi, Sikander

Blood | February 8, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 1-2

10.1182/blood-2020-139929 Get It

Introduction: Daratumumab (D) is an anti-CD38 monoclonal antibody, used frequently in combination with immunomodulatory drugs (IMiDs), lenalidomide (Len) and pomalidomide (Pom). There are no studies comparing DRd to DPd in Len-exposed or refractory multiple myeloma (MM). We present the Mayo Clinic experience of DPd and DRd utilization and outcomes. Methods: We identified consecutive MM pts who received D, between 1/2015 and 4/2019 at Mayo Clinic. We included pts who were exposed (at least one full cycle, 21/28 days) or refractory (progression on full dose or maintenance Len during treatment or within 60 days of stopping Len) to Len prior to D and received 1 to 4 prior lines of therapy. Only Pts who received DRd and DPd were included. Results: Out of 411 evaluable pts 162 met the inclusion criteria; 67 were Len exposed, but not refractory and 95 were Len refractory. Pts' characteristics are shown in Table 1. DRd was used in 76 (47%) and DPd in 86 (53%) pts. Majority of pts (105; 65%) received DPd or DRd in the 2nd or 3rd line and 104 pts (64%) are still alive. In Len refractory pts, the median time from last dose of Len to D initiation was 1 mths (interquartile range 0-6.5). Seventy pts (43%) had high-risk cytogenetics (HR). Only 11 pts (7%) underwent autologous hematopoietic cell transplant after DPd or DRd regimen. There was no significant difference between pts who received DRd and DPd in terms of age (>65 years), gender, race, proportion exposed or refractory to Bortezomib, number of prior lines of treatment (>2), or HR status (p>0.05 for all). Pts who received DPd were 4 times more likely to be Len refractory compared to pts who received DRd, p=0.0008. Median follow up time for the whole cohort from initial diagnosis was 92 mths (CI 95%; 79.5-107), while from D start date was 30 mths (CI 95%; 27-34). Median PFS for the whole cohort was 21 mths (CI 95%; 15-25) and median OS was 138 mths (CI 95%; 111-193). In Len exposed but not refractory pts, n=67, the overall response rate (ORR) was 82% in the DRd group compared to 68% in the DPd group, p=0.2. There was no difference in median PFS; 25.5 mths (CI 95%; 23-NR) for DRd compared to 25 mths (CI 95%; 5-NR) for DPd, p=0.37. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 138-NR) and 145.5 mths (CI 95%; 70-NR), respectively, p=0.06. In the 48 Len exposed but refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 39 mths (CI 95%; 23-NR) for DRd compared to 21 mths (CI 95%; 3-NR) for DPd, p=0.11. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; NR-NR) and 145.5 mths (CI 95%; 36-NR), respectively, p=0.13. In Len refractory pts only, n=95, the ORR was 84% in the DRd group compared to 58% in the DPd group, p=0.009. There was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 9 mths (CI 95%; 5-15) for DPd, p=0.18. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 78-NR) and 106 mths (CI 95%; 66-183), respectively, p=0.5. In the 57 Len refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 13 mths (CI 95%; 5-NR) for DPd, p=08. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 69-NR) and 105 mths (CI 95%; 47-NR), respectively, p=0.35. In the 16 Len exposed but not refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, the median PFS was better in the DRd group; 24.4 mths (CI 95%; 12-NR) compared to 3.3 mths (CI 95%; 1.9-27.5) for DPd, p=0.0093. However, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 51-NR) and NR mths (CI 95%; 18-NR), respectively, p=0.13. In the 29 Len refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, there was no statistically significant difference in median PFS; 18 mths (CI 95%; 6-43) for DRd compared to 6 mths (CI 95%; 4-13) for DPd, p=0.22.Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 47-NR) and 53 mths (CI 95%; 26-105), respectively, p=0.2. Conclusions: D+IMiD regimens after prior Len exposure/refractoriness are commonly used in real-world, despite the lack of data from prospective clinical trials. Combining D with IMiDs in Len exposed or refractory pts is efficacious, whether the IMiD is Len or Pom. Our study shows that regardless of prior Len use, DRd is at least equivalent to DPd. Prospective studies should be done to confirm these observations. Disclosures Alhaj Moustafa: Acrotech: Consultancy. Larsen:Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kapoor:Janssen: Research Funding; GlaxoSmithKline: Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding. Fonseca:Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Dingli:Karyopharm Therapeutics: Research Funding; Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy. Ailawadhi:Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria; Janssen: Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding.
Consolidation with Nivolumab and Brentuximab Vedotin after Autologous Hematopoietic Cell Transplantation in Patients with High-Risk Hodgkin Lymphoma
Herrera, Alex F. , Chen, Lu , Johnston, Patrick B. , Popplewell, Leslie , Cao, Thai M., Farol, Len, Sahebi, Firoozeh , Spielberger, Ricardo , Chen, Robert , Nademanee, Auayporn, Peters, Lacolle, Kennedy, Neena, Forman, Stephen J. , Feldman, Tatyana , Nieto, Yago , Holmberg, Leona , Mei, Matthew , Armenian, Saro H. , Rosen, Steven T. , Kwak, Larry W.

Blood | February 6, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 19-20

10.1182/blood-2020-136384 Get It

Introduction: Standard of care for patients (pts) with relapsed or refractory (RR) Hodgkin lymphoma (HL) is salvage therapy (tx) followed by autologous hematopoietic cell transplantation (HCT). However, most pts with high-risk RR HL will relapse after HCT. The AETHERA study demonstrated that post-HCT consolidation with brentuximab vedotin (BV) in high-risk HL pts improved progression-free survival (PFS) compared to placebo, particularly in pts with 2+ risk factors (Moskowitz, 2018). Pts with prior BV exposure were excluded from AETHERA, and BV is increasingly used prior to HCT in HL. PD1 blockade is effective in pts with RR HL and PD1 monotherapy as post-HCT consolidation in HL resulted in promising 18 mo PFS (Armand, 2019). Combined BV and nivolumab (Nivo) is a safe and effective salvage tx in HL, therefore we conducted a multicenter phase 2 study to evaluate the safety and efficacy of BV-Nivo post-HCT consolidation in high risk RR HL. Methods: After HCT, adult pts with high-risk HL defined as having ≥ 1 of the following modified AETHERA risk factors were eligible: primary refractory HL, relapse < 1 year of completing initial tx, extranodal disease (dz) at relapse, B symptoms (sx) at relapse, requiring > 1 salvage tx, not in CR at HCT. Prior BV or PD1 blockade were allowed if pts were not refractory. Pts underwent HCT according to institutional standards at the 5 centers. Starting between day 30-75 after HCT, pts received 1.8 mg/kg of BV and 3mg/kg nivo q21 days for a planned 8 cycles. If 1 drug was discontinued due to toxicity, the other could be continued. Investigators assessed response and progressive disease (PD) according to the 2014 Lugano classification. The primary endpoint was 18 mo PFS from study tx initiation. Secondary endpoints were overall survival (OS), safety, and the response rate in pts not in complete response (CR) at baseline. Results: 59 pts were enrolled and treated with at least one dose of study tx. Baseline characteristics are listed in Table 1. 18 (31%) pts were primary refractory, 35 (59%) had early relapse, 23 (39%) had extranodal dz and 14 (24%) had B sx at relapse, 15 (25%) received > 1 salvage tx before HCT, and 48 (81%) were in CR at HCT. 21 (36%) had 1 modified AETHERA risk factor, 23 (40%) had 2 and 14 (24%) had 3+ risk factors. The median follow-up time from study tx initiation was 15.7 months (range, 2.8-35.5). Patients initiated BV-nivo a median 54 days from HCT (range, 34-75) and received a median of 8 cycles (range, 1-8). 29 (49%) pts completed all 8 cycles of BV and nivo and 45 (76%) patients completed 8 cycles of one drug. 14 (24%) pts discontinued both BV and nivo early, including 6 for adverse events (AE), 6 pt withdrawals, 1 pt lost to follow-up, and 1 pt death from PJP pneumonia unrelated to study tx. BV was discontinued in 8 (14%) pts - due to grade (gr) 3 peripheral neuropathy (PN) in 2 pts, gr 2 PN in 2 pts, carpal tunnel syndrome in 1 pt, gastrointestinal AEs in 2 pts, and infusion related reaction in 1 pt. Nivo was discontinued in 7 (12%) pts - due to pneumonitis in 2 pts, and colitis, elevated bilirubin, abnormal transaminases, pneumonia with elevated creatinine, and hypotension with fever in 1 pt each. BV was dose reduced to 1.2mg/kg in 11 (19%) pts, 9 pts for PN, and 1 each for neutropenia and arthralgia. The most common AEs related to BV-Nivo consolidation were PN (51%, 3% gr 3), neutropenia (42%, 31% gr 3-4), fatigue (37%), diarrhea (29%, 3% gr 3), nausea (25%, 2% gr 3), arthralgia (24%), AST elevation (24%, 2% gr 3). The most frequent gr 3-4 AEs were neutropenia (31%), pneumonitis (7%), and ALT elevation (5%). Immune-related (ir) AEs requiring systemic corticosteroids occurred in 18 (31%) patients. Most common Gr 2 or higher irAEs included: pneumonitis (12%), AST or ALT elevation (8%), hypothyroidism (5%), and rash (3%). 6 pts were not in CR at baseline after HCT (all PR). 5 pts converted to CR with study tx and 1 pt remained in PR without PD. There were only 2 PFS events, 1 pt with relapse at 15 months and PJP-related death after prophylaxis was self-discontinued. The estimated 18 mo PFS and OS in all patients were 95% and 98%, respectively. The estimated 18 mo PFS in pts with 2+ and 3+ risk factors were 92% and 89%, respectively. Conclusions: Post-HCT consolidation with BV-Nivo in pts with high-risk RR HL is a promising approach, with only 1 relapse observed in our cohort with short follow-up thus far. Post-HCT BV-Nivo was tolerable, though IrAEs were observed more frequently than in the pre-HCT setting and PN and neutropenia were common. Disclosures Herrera: Pharmacyclics: Research Funding; Karyopharm: Consultancy; AstraZeneca: Research Funding; Gilead Sciences: Consultancy, Research Funding; Immune Design: Research Funding; Seattle Genetics: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding. Nieto:Affimed: Consultancy, Other: Grant Support; Secura Bio: Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support. Holmberg:Sanofi: Research Funding; Seattle Genetics: Research Funding; Millenium-Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; UpToDate: Patents & Royalties: Royalties; Janssen: Research Funding; Merck: Research Funding. Mei:Sanofi: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees. Chen:Autolus Therapeutics: Current Employment. Rosen:Abbvie: Speakers Bureau; Seattle Genetics: Consultancy; NeoGenomics: Consultancy; Aileron Therapeutics: Consultancy; Novartis: Consultancy; Pebromene: Consultancy; Celgene: Speakers Bureau; paradigm Medical Communications: Speakers Bureau. Kwak:CJ Healthcare: Consultancy; Xeme Biopharma/Theratest: Other: equity; Sellas Life Sciences Grp: Consultancy; Enzychem Life Sciences: Membership on an entity's Board of Directors or advisory committees; Antigenics: Other: equity; InnoLifes, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pepromene Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion Healthcare: Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Consultancy. Feldman:Portola: Research Funding; Pfizer: Research Funding; Kyowa Kirin: Consultancy, Research Funding; Eisai: Research Funding; Cell Medica: Research Funding; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Trillium: Research Funding; Janssen: Speakers Bureau; Viracta: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; AstraZeneca: Consultancy. OffLabel Disclosure: Nivolumab is not FDA-approved for use as consolidation after autologous stem cell transplantation