PHASE II RANDOMIZED CLINICAL TRIAL COMPARING ROPEGINTERFERON VERSUS PHLEBOTOMY IN LOW-RISK PATIENTS WITH POLYCYTHEMIA VERA. RESULTS OF THE PRE-PLANNED INTERIM ANALYSIS
Author(s): ,
Tiziano Barbui
Affiliations:
FROM Research Foundation,Bergamo,Italy
,
Alessandro Maria Vannucchi
Affiliations:
CRIMM,A.O.U. Careggi - Università di Firenze,Firenze,Italy
,
Valerio De Stefano
Affiliations:
Dipartimento di Scienze Radiologiche ed Ematologiche, Sezione di Ematologia,Università Cattolica del Sacro Cuore - Policlinico Universitario A. Gemelli,Roma,Italy
,
Arianna Masciulli
Affiliations:
FROM Research Foundation,Bergamo,Italy
,
Alessandra Carobbio
Affiliations:
FROM Research Foundation,Bergamo,Italy
,
Arianna Ghirardi
Affiliations:
FROM Research Foundation,Bergamo,Italy
,
Fabio Ciceri
Affiliations:
Unità Operativa di Ematologia e Trapianto Midollo Osseo,Ospedale San Raffaele,Milano,Italy
,
Massimiliano Bonifacio
Affiliations:
Unità di Ematologia,Ospedaliera Universitaria Integrata Verona,Verona,Italy
,
Alessandra Iurlo
Affiliations:
UOC Ematologia,Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico,Milano,Italy
,
Francesca Palandri
Affiliations:
Institute of Hematology 'L. and A. Seràgnoli',S. Orsola-Malpighi University hospital,Bologna,Italy
,
Giulia Benevolo
Affiliations:
S.C. Ematologia,A.O.U. Città della Salute e della Scienza di Torino – Presidio Ospedaliero Molinette,Torino,Italy
,
Fabrizio Pane
Affiliations:
UOC di Ematologia e Trapianti di Midollo ,A.O.U. Federico II di Napoli, Università di Napoli Federico II,Napoli,Italy
,
Alessandra Ricco
Affiliations:
U.O. Ematologia con Trapianto ,A.O.U. 'Consorziale Policlinico' di Bari,Bari,Italy
,
Giuseppe Carli
Affiliations:
UOC Ematologia,Azienda ULSS 8 Berica Ospedale San Bortolo di Vicenza,Vicenza,Italy
,
Marianna Caramella
Affiliations:
Divisione di Ematologia,ASST Grande Ospedale Metropolitano Niguarda,Milano,Italy
,
Davide Rapezzi
Affiliations:
Divisione di Ematologia,Azienda Ospedaliera S. Croce e Carle di Cuneo,Cuneo,Italy
,
Caterina Musolino
Affiliations:
UOC Ematologia,A.O.U. Policlinico 'G. Martino',Messina,Italy
,
Sergio Siragusa
Affiliations:
Divisione di Ematologia,A.O.U. Policlinico 'P. Giaccone',Palermo,Italy
,
Elisa Rumi
Affiliations:
Divisione di Ematologia,Fondazione IRCCS Policlinico San Matteo Pavia,Pavia,Italy
,
Andrea Patriarca
Affiliations:
SCDU Ematologia,A.O.U. Maggiore della Carità,Novara,Italy
,
Nicola Cascavilla
Affiliations:
U.O. Ematologia,IRCCS 'Casa Sollievo della Sofferenza',San Giovanni Rotondo,Italy
,
Barbara Mora
Affiliations:
Divisione di Ematologia,ASST dei Sette Laghi,Varese,Italy
,
Emma Cacciola
Affiliations:
U.O.C. di Emostasi - Centro Federato F.C.S.A.,A.O.U. 'Policlinico – Vittorio Emanuele' – P.O. Gaspare Rodolico,Catania,Italy
,
Giuseppe Gaetano Loscocco
Affiliations:
CRIMM,A.O.U. Careggi - Università di Firenze,Firenze,Italy
,
Paola Guglielmelli
Affiliations:
CRIMM,A.O.U. Careggi - Università di Firenze,Firenze,Italy
,
Elena Rossi
Affiliations:
Dipartimento di Scienze Radiologiche ed Ematologiche, Sezione di Ematologia,Università Cattolica del Sacro Cuore - Policlinico Universitario A. Gemelli,Roma,Italy
,
Silvia Betti
Affiliations:
Dipartimento di Scienze Radiologiche ed Ematologiche, Sezione di Ematologia,Università Cattolica del Sacro Cuore - Policlinico Universitario A. Gemelli,Roma,Italy
,
Francesca Lunghi
Affiliations:
Unità Operativa di Ematologia e Trapianto Midollo Osseo,Ospedale San Raffaele,Milano,Italy
,
Luigi Scaffidi
Affiliations:
Unità di Ematologia,Ospedaliera Universitaria Integrata Verona,Verona,Italy
,
Cristina Bucelli
Affiliations:
UOC Ematologia,Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico,Milano,Italy
,
Nicola Vianelli
Affiliations:
Institute of Hematology “L. and A. Seràgnoli”,S. Orsola-Malpighi University hospital,Bologna,Italy
,
Marta Bellini
Affiliations:
UOC Ematologia,ASST Papa Giovanni XXIII,Bergamo,Italy
Alessandro Rambaldi
Affiliations:
UOC Ematologia,ASST Papa Giovanni XXIII,Bergamo,Italy;Dipartimento di Oncologia-Ematologia,Università degli Studi di Milano,Milano,Italy
EHA Library. Barbui T. 06/14/20; 303391; LB2602
Tiziano Barbui
Tiziano Barbui
Contributions
Abstract

Abstract: LB2602

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Late-breaking Oral Session

Background
Phlebotomy represents the only cytoreductive procedure in low-risk patients with polycythemia vera (PV) (age <60 years and no history of thrombosis) to avoid the detrimental effect of blood hyperviscosity, thereby reducing the risk of cardiovascular complications. However, whether in low-risk patients, phlebotomies alone are adequate to keep haematocrit (HCT) on target level of 45% or less, or cytoreductive drugs should be added to reduce the still elevated risk of thrombosis, remains unexplored.

Aims
To report the results of a pre-planned interim analysis of Low-PV, a phase II investigator driven randomized trial (NCT030030025) conducted to assess the benefit/risk profile of Ropeginterferon alfa-2b versus phlebotomy alone (standard therapy) in low-risk patients with PV.

Methods
The present interim analysis was performed in 100 patients (two thirds of the pre-planned 150) followed-up for 1 year. Ropeginterferon administered subcutaneously (100 micrograms) every 2 weeks was compared with a stringent monthly phlebotomy program. The composite primary endpoint was defined by the percentage of patients maintaining the median HCT values ≤ 45% during 12 months, in the absence of progressive disease (i.e. thrombosis, bleeding, progressive leukocytosis, symptomatic or extreme thrombocytosis, symptomatic splenomegaly or other uncontrolled symptoms). Secondary end-points were number of phlebotomies, reduction of splenomegaly, leukocyte and platelet counts, iron deficiency, JAK2V617F allele burden and symptoms. Safety assessments were done at each monthly visit and included clinically relevant adverse events (AEs) as defined according to Common Terminology Criteria.

Results

The primary composite endpoint was reached in 84% of cases on Ropeginterferon vs. 60% in the standard arm (Odds Ratio=3.5, 95% CI: 1.3-10.4, p=0.008) and included patients who maintained the HCT target (84% vs. control 66%, p=0.038) and those without disease progression, which occurred in standard arm only (8%) (Figure 1). This result allowed to stop the trial early for overwhelming efficacy, preserving the overall two-sided type I error rate for effectiveness at the 0.05 level. Thus, the steering committee and the DSMB decided to stop the enrolment of new patients yet continuing the 2-years follow-up, as for protocol.

Albeit secondary endpoints will be evaluated at the end of the trial, preliminary results showed that the total number of phlebotomies after 1 year was higher in the standard arm (57%) than in the Ropeginterferon arm (43%) and the difference was most evident starting 6 months after the drug exposure (p=0.024). Improvements in symptoms, as assessed by using the MPN symptom-assessment form, were seen in 7 out of 10 items (mean change -21%) in the Ropeginterferon arm whereas a worsening in half of items was noted in the standard arm (mean change +10%) (p=0.033). Among the other valuable secondary end-points, Ropeginterferon was associated with significant reduction of splenomegaly and leukocyte and platelet counts.

In regard to safety, there was no difference in grade >3 AEs, which accounted for 6% and 8% of patients treated with Ropeginterferon or standard therapy, respectively.



Conclusion
This interim analysis of Low-PV trial convincingly demonstrated that Ropeginterferon is safe and more efficacious in keeping HCT on target in low-risk PV patients. This result has been achieved with a reduction in the number of phlebotomies and with an improvement in the quality of life.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Clinical trial, Interferon alpha, Phase II, Polycythemia vera

Abstract: LB2602

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Late-breaking Oral Session

Background
Phlebotomy represents the only cytoreductive procedure in low-risk patients with polycythemia vera (PV) (age <60 years and no history of thrombosis) to avoid the detrimental effect of blood hyperviscosity, thereby reducing the risk of cardiovascular complications. However, whether in low-risk patients, phlebotomies alone are adequate to keep haematocrit (HCT) on target level of 45% or less, or cytoreductive drugs should be added to reduce the still elevated risk of thrombosis, remains unexplored.

Aims
To report the results of a pre-planned interim analysis of Low-PV, a phase II investigator driven randomized trial (NCT030030025) conducted to assess the benefit/risk profile of Ropeginterferon alfa-2b versus phlebotomy alone (standard therapy) in low-risk patients with PV.

Methods
The present interim analysis was performed in 100 patients (two thirds of the pre-planned 150) followed-up for 1 year. Ropeginterferon administered subcutaneously (100 micrograms) every 2 weeks was compared with a stringent monthly phlebotomy program. The composite primary endpoint was defined by the percentage of patients maintaining the median HCT values ≤ 45% during 12 months, in the absence of progressive disease (i.e. thrombosis, bleeding, progressive leukocytosis, symptomatic or extreme thrombocytosis, symptomatic splenomegaly or other uncontrolled symptoms). Secondary end-points were number of phlebotomies, reduction of splenomegaly, leukocyte and platelet counts, iron deficiency, JAK2V617F allele burden and symptoms. Safety assessments were done at each monthly visit and included clinically relevant adverse events (AEs) as defined according to Common Terminology Criteria.

Results

The primary composite endpoint was reached in 84% of cases on Ropeginterferon vs. 60% in the standard arm (Odds Ratio=3.5, 95% CI: 1.3-10.4, p=0.008) and included patients who maintained the HCT target (84% vs. control 66%, p=0.038) and those without disease progression, which occurred in standard arm only (8%) (Figure 1). This result allowed to stop the trial early for overwhelming efficacy, preserving the overall two-sided type I error rate for effectiveness at the 0.05 level. Thus, the steering committee and the DSMB decided to stop the enrolment of new patients yet continuing the 2-years follow-up, as for protocol.

Albeit secondary endpoints will be evaluated at the end of the trial, preliminary results showed that the total number of phlebotomies after 1 year was higher in the standard arm (57%) than in the Ropeginterferon arm (43%) and the difference was most evident starting 6 months after the drug exposure (p=0.024). Improvements in symptoms, as assessed by using the MPN symptom-assessment form, were seen in 7 out of 10 items (mean change -21%) in the Ropeginterferon arm whereas a worsening in half of items was noted in the standard arm (mean change +10%) (p=0.033). Among the other valuable secondary end-points, Ropeginterferon was associated with significant reduction of splenomegaly and leukocyte and platelet counts.

In regard to safety, there was no difference in grade >3 AEs, which accounted for 6% and 8% of patients treated with Ropeginterferon or standard therapy, respectively.



Conclusion
This interim analysis of Low-PV trial convincingly demonstrated that Ropeginterferon is safe and more efficacious in keeping HCT on target in low-risk PV patients. This result has been achieved with a reduction in the number of phlebotomies and with an improvement in the quality of life.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Clinical trial, Interferon alpha, Phase II, Polycythemia vera

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