EXCELLENT LONG-TERM PROGNOSIS OF IMATINIB-TREATED FIP1L1-PDGFRA POSITIVE EOSINOPHILIA-ASSOCIATED MYELOPROLIFERATIVE NEOPLASM IN CHRONIC OR BLAST PHASE
(Abstract release date: 05/21/15)
EHA Library. Metzgeroth G. 06/13/15; 103077; S449
Disclosure(s): UNIVERSITÄTSKLINIKUM MANNHEIMMedizinische Klinik III
Prof. Dr. Georgia Metzgeroth
Contributions
Contributions
Abstract
Abstract: S449
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:15 to 13.06.2015 12:30
Location: Room A8
Background
Aims
To evaluate the long-term prognosis of FP+ pts in CP or BP on imatinib.
Methods
Results
In CP, complete molecular remission (CMR) was observed after 6, 12 and 24 months in 26/48 (54%), 35/42 (83%) and 38/39 (97%) of pts, respectively, as investigated by qualitative nested RT-PCR. The median duration of CMR was 73 months (range 3-129). Imatinib was reduced to 2-3 x 100mg/week in 15 pts for a median of 28 months (range 1-96) and no relapse has yet been observed. Imatinib was stopped in 4 pts with 3 pts remaining in CMR for 2, 19 and 20 months, respectively. One patient relapsed after 12 months but rapidly achieved second CMR after rechallenge with imatinib. In BP, imatinib was used as monotherapy (n=7) or after intensive chemotherapy (n=5). All pts achieved durable CMR (median 95 months, range 66-132). Overall, imatinib was well tolerated and no grade III-IV toxicities were observed. At the time of analysis, 3 pts had died (CP, n=1; BP, n=2) but no death was disease- or treatment-related. Two pts developed a secondary resistance, 7 and 10 months after start of imatinib. A T674I point mutation in the ATP-binding domain of FIP1L1-PDGFRA was identified in one patient while the mechanism of resistance in the second patient remained unknown. Because treatment with nilotinib and/or sorafenib did not result in significant remissions, both pts received an allogeneic stem cell transplantation (SCT) 5 and 8 months, respectively, after detection of imatinib-resistance. Both pts achieved a rapid complete hematologic remission. One patient has been in stable CMR for 48 months while the second patient died 18 months after SCT in ongoing CMR.
Summary
Treatment with imatinib in FP+ MPN-eo is associated with an excellent long-term prognosis, even if pts are initially diagnosed in myeloid or lymphoid BP. Complete remissions are rapidly achieved, are durable and can be maintained with low-dose imatinib. Discontinuation of imatinib may be feasible in some cases. Primary resistance has not yet been reported and secondary resistance seems to be very rare. If it occurs, the efficacy of second-generation tyrosine kinase inhibitors seems to be poor. Eligible pts should therefore be offered an allogeneic SCT.
Keyword(s): Eosinophilia, FIP1L1-PDGFRA, Imatinib
Session topic: MPN: Prognosis and treatment
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:15 to 13.06.2015 12:30
Location: Room A8
Background
FIP1L1-PDGFRA (FP) is the most common fusion gene in eosinophilia-associated myeloproliferative neoplasms (MPN-eo) and is exquisitely sensitive to treatment with imatinib. The vast majority of FP positive (FP+) patients (pts) are diagnosed in chronic phase (CP) but rarely also in myeloid or lymphoid blast phase (BP).
Aims
To evaluate the long-term prognosis of FP+ pts in CP or BP on imatinib.
Methods
Here we present the long-term follow-up of 62 imatinib-treated FP+ pts in CP (n=50) or BP (n=12). Median age was 49 years (range 19-70) with a striking male predominance (61/62, 98%). All pts were treated with imatinib (100-400mg/d) for a median of 79 months (range 2-140).
Results
In CP, complete molecular remission (CMR) was observed after 6, 12 and 24 months in 26/48 (54%), 35/42 (83%) and 38/39 (97%) of pts, respectively, as investigated by qualitative nested RT-PCR. The median duration of CMR was 73 months (range 3-129). Imatinib was reduced to 2-3 x 100mg/week in 15 pts for a median of 28 months (range 1-96) and no relapse has yet been observed. Imatinib was stopped in 4 pts with 3 pts remaining in CMR for 2, 19 and 20 months, respectively. One patient relapsed after 12 months but rapidly achieved second CMR after rechallenge with imatinib. In BP, imatinib was used as monotherapy (n=7) or after intensive chemotherapy (n=5). All pts achieved durable CMR (median 95 months, range 66-132). Overall, imatinib was well tolerated and no grade III-IV toxicities were observed. At the time of analysis, 3 pts had died (CP, n=1; BP, n=2) but no death was disease- or treatment-related. Two pts developed a secondary resistance, 7 and 10 months after start of imatinib. A T674I point mutation in the ATP-binding domain of FIP1L1-PDGFRA was identified in one patient while the mechanism of resistance in the second patient remained unknown. Because treatment with nilotinib and/or sorafenib did not result in significant remissions, both pts received an allogeneic stem cell transplantation (SCT) 5 and 8 months, respectively, after detection of imatinib-resistance. Both pts achieved a rapid complete hematologic remission. One patient has been in stable CMR for 48 months while the second patient died 18 months after SCT in ongoing CMR.
Summary
Treatment with imatinib in FP+ MPN-eo is associated with an excellent long-term prognosis, even if pts are initially diagnosed in myeloid or lymphoid BP. Complete remissions are rapidly achieved, are durable and can be maintained with low-dose imatinib. Discontinuation of imatinib may be feasible in some cases. Primary resistance has not yet been reported and secondary resistance seems to be very rare. If it occurs, the efficacy of second-generation tyrosine kinase inhibitors seems to be poor. Eligible pts should therefore be offered an allogeneic SCT.
Keyword(s): Eosinophilia, FIP1L1-PDGFRA, Imatinib
Session topic: MPN: Prognosis and treatment
Abstract: S449
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:15 to 13.06.2015 12:30
Location: Room A8
Background
Aims
To evaluate the long-term prognosis of FP+ pts in CP or BP on imatinib.
Methods
Results
In CP, complete molecular remission (CMR) was observed after 6, 12 and 24 months in 26/48 (54%), 35/42 (83%) and 38/39 (97%) of pts, respectively, as investigated by qualitative nested RT-PCR. The median duration of CMR was 73 months (range 3-129). Imatinib was reduced to 2-3 x 100mg/week in 15 pts for a median of 28 months (range 1-96) and no relapse has yet been observed. Imatinib was stopped in 4 pts with 3 pts remaining in CMR for 2, 19 and 20 months, respectively. One patient relapsed after 12 months but rapidly achieved second CMR after rechallenge with imatinib. In BP, imatinib was used as monotherapy (n=7) or after intensive chemotherapy (n=5). All pts achieved durable CMR (median 95 months, range 66-132). Overall, imatinib was well tolerated and no grade III-IV toxicities were observed. At the time of analysis, 3 pts had died (CP, n=1; BP, n=2) but no death was disease- or treatment-related. Two pts developed a secondary resistance, 7 and 10 months after start of imatinib. A T674I point mutation in the ATP-binding domain of FIP1L1-PDGFRA was identified in one patient while the mechanism of resistance in the second patient remained unknown. Because treatment with nilotinib and/or sorafenib did not result in significant remissions, both pts received an allogeneic stem cell transplantation (SCT) 5 and 8 months, respectively, after detection of imatinib-resistance. Both pts achieved a rapid complete hematologic remission. One patient has been in stable CMR for 48 months while the second patient died 18 months after SCT in ongoing CMR.
Summary
Treatment with imatinib in FP+ MPN-eo is associated with an excellent long-term prognosis, even if pts are initially diagnosed in myeloid or lymphoid BP. Complete remissions are rapidly achieved, are durable and can be maintained with low-dose imatinib. Discontinuation of imatinib may be feasible in some cases. Primary resistance has not yet been reported and secondary resistance seems to be very rare. If it occurs, the efficacy of second-generation tyrosine kinase inhibitors seems to be poor. Eligible pts should therefore be offered an allogeneic SCT.
Keyword(s): Eosinophilia, FIP1L1-PDGFRA, Imatinib
Session topic: MPN: Prognosis and treatment
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:15 to 13.06.2015 12:30
Location: Room A8
Background
FIP1L1-PDGFRA (FP) is the most common fusion gene in eosinophilia-associated myeloproliferative neoplasms (MPN-eo) and is exquisitely sensitive to treatment with imatinib. The vast majority of FP positive (FP+) patients (pts) are diagnosed in chronic phase (CP) but rarely also in myeloid or lymphoid blast phase (BP).
Aims
To evaluate the long-term prognosis of FP+ pts in CP or BP on imatinib.
Methods
Here we present the long-term follow-up of 62 imatinib-treated FP+ pts in CP (n=50) or BP (n=12). Median age was 49 years (range 19-70) with a striking male predominance (61/62, 98%). All pts were treated with imatinib (100-400mg/d) for a median of 79 months (range 2-140).
Results
In CP, complete molecular remission (CMR) was observed after 6, 12 and 24 months in 26/48 (54%), 35/42 (83%) and 38/39 (97%) of pts, respectively, as investigated by qualitative nested RT-PCR. The median duration of CMR was 73 months (range 3-129). Imatinib was reduced to 2-3 x 100mg/week in 15 pts for a median of 28 months (range 1-96) and no relapse has yet been observed. Imatinib was stopped in 4 pts with 3 pts remaining in CMR for 2, 19 and 20 months, respectively. One patient relapsed after 12 months but rapidly achieved second CMR after rechallenge with imatinib. In BP, imatinib was used as monotherapy (n=7) or after intensive chemotherapy (n=5). All pts achieved durable CMR (median 95 months, range 66-132). Overall, imatinib was well tolerated and no grade III-IV toxicities were observed. At the time of analysis, 3 pts had died (CP, n=1; BP, n=2) but no death was disease- or treatment-related. Two pts developed a secondary resistance, 7 and 10 months after start of imatinib. A T674I point mutation in the ATP-binding domain of FIP1L1-PDGFRA was identified in one patient while the mechanism of resistance in the second patient remained unknown. Because treatment with nilotinib and/or sorafenib did not result in significant remissions, both pts received an allogeneic stem cell transplantation (SCT) 5 and 8 months, respectively, after detection of imatinib-resistance. Both pts achieved a rapid complete hematologic remission. One patient has been in stable CMR for 48 months while the second patient died 18 months after SCT in ongoing CMR.
Summary
Treatment with imatinib in FP+ MPN-eo is associated with an excellent long-term prognosis, even if pts are initially diagnosed in myeloid or lymphoid BP. Complete remissions are rapidly achieved, are durable and can be maintained with low-dose imatinib. Discontinuation of imatinib may be feasible in some cases. Primary resistance has not yet been reported and secondary resistance seems to be very rare. If it occurs, the efficacy of second-generation tyrosine kinase inhibitors seems to be poor. Eligible pts should therefore be offered an allogeneic SCT.
Keyword(s): Eosinophilia, FIP1L1-PDGFRA, Imatinib
Session topic: MPN: Prognosis and treatment
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