Clinical prognostic markers in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature B lymphocytes in blood, bone marrow and lymphoid tissues. The clinical course for the individual patient is still unpredictable despite decades of research on prognostic markers and staging systems. The aim of this thesis was to review the value of existing prognostic tools in order to develop new clinical prognostic markers for CLL and to assess the impact of clonal evolution and transformation in CLL in relation to biological markers and given therapy. Paper I: This is a long-term follow-up of the first trial of subcutaneous alemtuzumab as firstline therapy in CLL. In order to assess duration of response, infectious complications and incidence of Richter transformation, a comparison was made with historical controls. Median time to treatment failure was 28 months for the alemtuzumab-treated patients compared to 17 months for the control group (not significant). Infectious complications were not more common in the alemtuzumab-treated patients despite profound and prolonged T-cell suppression. The rate of Richter transformation was similar between the groups. Paper II: Clinical data of 77 patients included in five phase II trials at Karolinska University Hospital were analyzed to find out whether the use of computed tomography (CT) could add prognostic information to the Rai and Binet clinical staging systems. A high nodal tumor burden evaluated by CT correlated with a shorter time to next therapy and a trend towards shorter survival. Massive splenomegaly was associated with shorter overall survival and therapy-free survival. Paper III: The expression of the estrogen receptors (ER) α, β1 and its splice variant β2 was evaluated in peripheral blood mononuclear cells (PBMC) from CLL patients and normal controls using immunocytochemistry. The expression of ERα was generally low whereas most PBMCs expressed ERβ1 in both patients and controls. ERβ2 expression was significantly more common in CLL. Patients with high expression (> 50% of PBMC) of ERβ1 and/or ERβ2 were more likely to need therapy during follow-up. Paper IV: Paraffin-embedded splenic tissue samples were obtained from 62 patients with CLL or SLL to assess whether chromosomal aberrations in the spleen have a prognostic impact. The cytogenetic abnormalities 11q-, 13q-, 17p- and trisomy 12 were assessed by interphase FISH and compared with samples from blood and/or bone marrow. Patients with 11q- and 17p- deletions in the spleen had significantly shorter overall and therapy-free survival. Clonal evolution seemed to occur in some cases

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma:Analyses From Longer Follow-up of the OCEAN and HORIZON Studies

Introduction: Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN. Methods: These analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022). Results: In OCEAN, subgroups prognostic for OS were age (P = .011; &lt;65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression &gt;36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed &lt;36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed &lt;36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports. Conclusion: These analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed &gt;36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).</p

Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group

Ibrutinib, a Brutons tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine healthcare are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy amp;gt;= 10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richters transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia.Funding Agencies|Swedish Cancer Society [15 0894]; Cancer Society in Stockholm [144142, 151313]; King Gustav V Jubilee Fund [144193]; Cancer and Allergy Foundation [150 420, 150 431]; StratCan Karolinska Institutet [2201]; AFA Insurance [130054]; Stockholm County Council, Sweden [20150070]</p

Long-term real-world results of ibrutinib therapy in patients with relapsed or refractory chronic lymphocytic leukemia : 30-month follow up of the Swedish compassionate use cohort

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Recensioner

Book reviews: Herbert W. Basser with Marsha B. Cohen The Gospel of Matthew and Judaic Traditions: A Relevance-based Commentary (Tobias Ålöw) Alicia J. Batten och John S. Kloppenborg (red.) James, 1 &amp; 2 Peter, and Early Jesus Traditions (Leonhard Franke) Bible Works 10  (Bo Krister Ljungberg) Derek R. Brown The God of This Age: Satan in the Churches and Letters of the Apostle Paul (Torsten Löfstedt) William P. Brown (ed.) The Oxford Handbook of the Psalms  (David Willgren) Constantine R. Campbell Advances in the Study of Greek: New Insights for Reading the New Testament  (Jan H. Nylund) Nancy L. deClaissé-Walford (ed.)  The Shape and Shaping of the Book of Psalms: The Current State of Scholarship (David Willgren) Nancy L. deClaissé-Walford, Rolf A. Jacobson and Beth Laneel Tanner  The Book of Psalms (David Willgren) Thomas B. Dozeman, Konrad Schmid och Baruch J. Schwartz (red.)  The Pentateuch: International Perspectives on Current Research (Stig Norin) Ole Jakob Filtvedt The Identity of God’s People and the Paradox of Hebrews (Mikael Tellbe) David Hellholm, Tor Vegge, Øyvind Norderval and Christer Hellholm (eds.) Ablution, Initiation, and Baptism: Late Antiquity, Early Judaism, and Early Christianity (James A. Kelhoffer) Wesley Hill  Paul and the Trinity: Persons, Relations, and the Pauline Letters (Mikael Tellbe) Douglas S. Huffman Verbal Aspect Theory and the Prohibitions in the Greek New Testament (Jan H. Nylund) Thomas Kazen Scripture, Interpretation, or Authority? Motives and Arguments in Jesus’ Halakic Conflicts (Cecilia Wassén) Judith M. Lieu Marcion and the Making of a Heretic: God and Scripture in the Second Century (James A. Kelhoffer) L. Michael Morales (ed.) Cult and Cosmos: Tilting Toward a Temple-Centered Theology (Stefan Green) Mark D. Nanos och Magnus Zetterholm (red.) Paul within Judaism: Restoring the First-Century Context to the Apostle (Martin Landgren) Carol A. Newsom och Brennan W. Breed Daniel: A Commentary (LarsOlov Eriksson) Maren Niehoff (red.) Homer and the Bible in the Eyes of Ancient Interpreters (Blazenka Scheuer) Kurt L. Noll Canaan and Israel in Antiquity: A Textbook on History and Religion (Richard Pleijel) Ken Parry (ed.)  The Wiley Blackwell Companion to Patristics (Carl Johan Berglund) Ralf Rothenbusch “... abgesondert zur Tora Gottes hin”: Ethnisch-religiöse Identitäten im Esra/Nehemiabuch (Lena-Sofia Tiemeyer) Michael L. Satlow How the Bible Became Holy (Martin Wessbrandt) Birke Siggelkow-Berner Die jüdischen Feste im Bellum Judaicum des Flavius Josephus (Birger Olsson) Lena-Sofia Tiemeyer och Hans M. Barstad (red.) Continuity and Discontinuity: Chronological and Thematic Development in Isaiah 40–66 (Stefan Green) W. Dennis Tucker Jr. Constructing and Deconstructing Power in Psalms 107–150 (David Willgren) Helmut Utzschneider och Wolfgang Oswald Exodus 1–15 (LarsOlov Eriksson) Urban C. Von Wahlde The Gospel and Letters of John, vol. 1:Introduction, Analysis, and Reference  The Gospel and Letters of John, vol. 2: Commentary on the Gospel of John The Gospel and Letters of John, vol. 3: Commentary on the Three Johannine Letters (Birger Olsson) Benjamin L. White Remembering Paul: Ancient and Modern Contests over the Image of the Apostle (Martin Wessbrandt

Recensioner

Book reviews: Herbert W. Basser with Marsha B. Cohen The Gospel of Matthew and Judaic Traditions: A Relevance-based Commentary (Tobias Ålöw) Alicia J. Batten och John S. Kloppenborg (red.) James, 1 &amp; 2 Peter, and Early Jesus Traditions (Leonhard Franke) Bible Works 10  (Bo Krister Ljungberg) Derek R. Brown The God of This Age: Satan in the Churches and Letters of the Apostle Paul (Torsten Löfstedt) William P. Brown (ed.) The Oxford Handbook of the Psalms  (David Willgren) Constantine R. Campbell Advances in the Study of Greek: New Insights for Reading the New Testament  (Jan H. Nylund) Nancy L. deClaissé-Walford (ed.)  The Shape and Shaping of the Book of Psalms: The Current State of Scholarship (David Willgren) Nancy L. deClaissé-Walford, Rolf A. Jacobson and Beth Laneel Tanner  The Book of Psalms (David Willgren) Thomas B. Dozeman, Konrad Schmid och Baruch J. Schwartz (red.)  The Pentateuch: International Perspectives on Current Research (Stig Norin) Ole Jakob Filtvedt The Identity of God’s People and the Paradox of Hebrews (Mikael Tellbe) David Hellholm, Tor Vegge, Øyvind Norderval and Christer Hellholm (eds.) Ablution, Initiation, and Baptism: Late Antiquity, Early Judaism, and Early Christianity (James A. Kelhoffer) Wesley Hill  Paul and the Trinity: Persons, Relations, and the Pauline Letters (Mikael Tellbe) Douglas S. Huffman Verbal Aspect Theory and the Prohibitions in the Greek New Testament (Jan H. Nylund) Thomas Kazen Scripture, Interpretation, or Authority? Motives and Arguments in Jesus’ Halakic Conflicts (Cecilia Wassén) Judith M. Lieu Marcion and the Making of a Heretic: God and Scripture in the Second Century (James A. Kelhoffer) L. Michael Morales (ed.) Cult and Cosmos: Tilting Toward a Temple-Centered Theology (Stefan Green) Mark D. Nanos och Magnus Zetterholm (red.) Paul within Judaism: Restoring the First-Century Context to the Apostle (Martin Landgren) Carol A. Newsom och Brennan W. Breed Daniel: A Commentary (LarsOlov Eriksson) Maren Niehoff (red.) Homer and the Bible in the Eyes of Ancient Interpreters (Blazenka Scheuer) Kurt L. Noll Canaan and Israel in Antiquity: A Textbook on History and Religion (Richard Pleijel) Ken Parry (ed.)  The Wiley Blackwell Companion to Patristics (Carl Johan Berglund) Ralf Rothenbusch “... abgesondert zur Tora Gottes hin”: Ethnisch-religiöse Identitäten im Esra/Nehemiabuch (Lena-Sofia Tiemeyer) Michael L. Satlow How the Bible Became Holy (Martin Wessbrandt) Birke Siggelkow-Berner Die jüdischen Feste im Bellum Judaicum des Flavius Josephus (Birger Olsson) Lena-Sofia Tiemeyer och Hans M. Barstad (red.) Continuity and Discontinuity: Chronological and Thematic Development in Isaiah 40–66 (Stefan Green) W. Dennis Tucker Jr. Constructing and Deconstructing Power in Psalms 107–150 (David Willgren) Helmut Utzschneider och Wolfgang Oswald Exodus 1–15 (LarsOlov Eriksson) Urban C. Von Wahlde The Gospel and Letters of John, vol. 1:Introduction, Analysis, and Reference  The Gospel and Letters of John, vol. 2: Commentary on the Gospel of John The Gospel and Letters of John, vol. 3: Commentary on the Three Johannine Letters (Birger Olsson) Benjamin L. White Remembering Paul: Ancient and Modern Contests over the Image of the Apostle (Martin Wessbrandt