Contributions
Abstract: PB1861
Type: Publication Only
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Richter syndrome is a transformation of chronic lymphocytic leukemia into DLBCL, occurring in about 2-15% of patients (pts) with CLL. These patients have a very poor prognosis with an unsatisfactory response to immunochemotherapy (R-XT) and a short overall survival. B-cell receptor signaling through Bruton tyrosine kinase (BTK) is one of the essential growth pathways for CLL. Acalabrutinib (highly selective BTK inhibitor) has shown significant efficacy in relapsed/refractory and untreated CLL.
Aims
improving the results of treatment of patients with Richter syndrome
Methods
we reported 4 cases of Richter syndrome treated with acalabrutinib + R-СТ.
Results
Table 1 shows the characteristics of 4 CLL pts who developed biopsy-proven DLBCL. The median time to transformation from CLL was 40,75 months (range 4-66). Clonality was not available testing in any pts. At the time of transformation, 2 pts were initially treated with R-CHOP with a suboptimal response, then acalabrutinib was added, 1 pt received 6 cycles of R-CHOP+ acalabrutinib and 1pt - 5 cycles R-CVP + acalabrutinib. The overall response (OR) was 75%:1 pt had a CR and 2 pts - PR. The pts who achieved OR are currently receiving acalabrutinib, 1 pt had progression of DLBCL after 15 months of acalabrutinib therapy. Acalabrutinib was well-tolerated; no patient required discontinuation as a result of adverse events.
At the time of CLL diagnosis (table1)
Age, y | 75 | 28 | 64 | 34 |
Sex | M | F | M | F |
Rai st. | II | II
| II
| II
|
CLL therapy Efficacy | Rituximab 2013 to 2015. CR | none | 6-G-FC in 2016 CR | 6 FCR in 2020 CR |
Time from CLL therapy to RS | 66m | 45m | 48m | 4m |
Localization of DLBCL | Peripheral, retroperitoneal lymph nodes, stomach | Lymph nodes, nasal sinuses, upper palate | Retroperitoneal lymph nodes, colon | Tumor of the tongue root |
DLBCL subtype | GCB | Non-GCB | Non-GCB | Non-GCB |
At the time of DLBCL diagnosis (table 1- continuation)
| 1 | 2 | 3 | 4 |
Age, y | 82 | 32 | 69 | 35 |
WBC ×109/L | 5,53 х10х9/L
| 6,23х10х9/L
| 10,25х10х9/L
| 0,840 х10х9/L
|
Hemoglobin, g/dL | 12,4 | 11,6 | 10,7 | 6,6 |
Platelet count ×109/L | 178,0 | 294,0 | 120,0 | 41,0 |
LDH, U/L | 322 | 196 | 410 | 317 |
IGHV mutation status | It is not possible to establish | Unmutated | Unmutated
| It is not possible to establish |
FISH | Normal | Normal | Normal | Normal |
Mutation TP53 | No mutations . | No mutations | No mutations | No mutations |
Mutation NOTCH1 | - | Mutation c7544 | No mutation | No mutation |
RS prognosis score | 2 (Intermediate) | 1 (Low) | 2 (Intermediate) | 1 (Low) |
Duration of acalabrutinib therapy (mon) | 15 | 12 | 15 | 5 |
Best response | PR | CR | Clinical benefit | PR |
Status at most recent follow-up | Аcalabrutinib therapy continues | Аcalabrutinib therapy continues | Death | Аcalabrutinib therapy continues |
Conclusion
our experience with these patients suggests that acalabrutinib in combination with immunochemotherapy has potential as a novel therapeutic approach for patients with Richter syndrome.
Keyword(s):
Abstract: PB1861
Type: Publication Only
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Richter syndrome is a transformation of chronic lymphocytic leukemia into DLBCL, occurring in about 2-15% of patients (pts) with CLL. These patients have a very poor prognosis with an unsatisfactory response to immunochemotherapy (R-XT) and a short overall survival. B-cell receptor signaling through Bruton tyrosine kinase (BTK) is one of the essential growth pathways for CLL. Acalabrutinib (highly selective BTK inhibitor) has shown significant efficacy in relapsed/refractory and untreated CLL.
Aims
improving the results of treatment of patients with Richter syndrome
Methods
we reported 4 cases of Richter syndrome treated with acalabrutinib + R-СТ.
Results
Table 1 shows the characteristics of 4 CLL pts who developed biopsy-proven DLBCL. The median time to transformation from CLL was 40,75 months (range 4-66). Clonality was not available testing in any pts. At the time of transformation, 2 pts were initially treated with R-CHOP with a suboptimal response, then acalabrutinib was added, 1 pt received 6 cycles of R-CHOP+ acalabrutinib and 1pt - 5 cycles R-CVP + acalabrutinib. The overall response (OR) was 75%:1 pt had a CR and 2 pts - PR. The pts who achieved OR are currently receiving acalabrutinib, 1 pt had progression of DLBCL after 15 months of acalabrutinib therapy. Acalabrutinib was well-tolerated; no patient required discontinuation as a result of adverse events.
At the time of CLL diagnosis (table1)
Age, y | 75 | 28 | 64 | 34 |
Sex | M | F | M | F |
Rai st. | II | II
| II
| II
|
CLL therapy Efficacy | Rituximab 2013 to 2015. CR | none | 6-G-FC in 2016 CR | 6 FCR in 2020 CR |
Time from CLL therapy to RS | 66m | 45m | 48m | 4m |
Localization of DLBCL | Peripheral, retroperitoneal lymph nodes, stomach | Lymph nodes, nasal sinuses, upper palate | Retroperitoneal lymph nodes, colon | Tumor of the tongue root |
DLBCL subtype | GCB | Non-GCB | Non-GCB | Non-GCB |
At the time of DLBCL diagnosis (table 1- continuation)
| 1 | 2 | 3 | 4 |
Age, y | 82 | 32 | 69 | 35 |
WBC ×109/L | 5,53 х10х9/L
| 6,23х10х9/L
| 10,25х10х9/L
| 0,840 х10х9/L
|
Hemoglobin, g/dL | 12,4 | 11,6 | 10,7 | 6,6 |
Platelet count ×109/L | 178,0 | 294,0 | 120,0 | 41,0 |
LDH, U/L | 322 | 196 | 410 | 317 |
IGHV mutation status | It is not possible to establish | Unmutated | Unmutated
| It is not possible to establish |
FISH | Normal | Normal | Normal | Normal |
Mutation TP53 | No mutations . | No mutations | No mutations | No mutations |
Mutation NOTCH1 | - | Mutation c7544 | No mutation | No mutation |
RS prognosis score | 2 (Intermediate) | 1 (Low) | 2 (Intermediate) | 1 (Low) |
Duration of acalabrutinib therapy (mon) | 15 | 12 | 15 | 5 |
Best response | PR | CR | Clinical benefit | PR |
Status at most recent follow-up | Аcalabrutinib therapy continues | Аcalabrutinib therapy continues | Death | Аcalabrutinib therapy continues |
Conclusion
our experience with these patients suggests that acalabrutinib in combination with immunochemotherapy has potential as a novel therapeutic approach for patients with Richter syndrome.
Keyword(s):
Abstract: PB1861
Type: Publication Only
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Richter syndrome is a transformation of chronic lymphocytic leukemia into DLBCL, occurring in about 2-15% of patients (pts) with CLL. These patients have a very poor prognosis with an unsatisfactory response to immunochemotherapy (R-XT) and a short overall survival. B-cell receptor signaling through Bruton tyrosine kinase (BTK) is one of the essential growth pathways for CLL. Acalabrutinib (highly selective BTK inhibitor) has shown significant efficacy in relapsed/refractory and untreated CLL.
Aims
improving the results of treatment of patients with Richter syndrome
Methods
we reported 4 cases of Richter syndrome treated with acalabrutinib + R-СТ.
Results
Table 1 shows the characteristics of 4 CLL pts who developed biopsy-proven DLBCL. The median time to transformation from CLL was 40,75 months (range 4-66). Clonality was not available testing in any pts. At the time of transformation, 2 pts were initially treated with R-CHOP with a suboptimal response, then acalabrutinib was added, 1 pt received 6 cycles of R-CHOP+ acalabrutinib and 1pt - 5 cycles R-CVP + acalabrutinib. The overall response (OR) was 75%:1 pt had a CR and 2 pts - PR. The pts who achieved OR are currently receiving acalabrutinib, 1 pt had progression of DLBCL after 15 months of acalabrutinib therapy. Acalabrutinib was well-tolerated; no patient required discontinuation as a result of adverse events.
At the time of CLL diagnosis (table1)
Age, y | 75 | 28 | 64 | 34 |
Sex | M | F | M | F |
Rai st. | II | II
| II
| II
|
CLL therapy Efficacy | Rituximab 2013 to 2015. CR | none | 6-G-FC in 2016 CR | 6 FCR in 2020 CR |
Time from CLL therapy to RS | 66m | 45m | 48m | 4m |
Localization of DLBCL | Peripheral, retroperitoneal lymph nodes, stomach | Lymph nodes, nasal sinuses, upper palate | Retroperitoneal lymph nodes, colon | Tumor of the tongue root |
DLBCL subtype | GCB | Non-GCB | Non-GCB | Non-GCB |
At the time of DLBCL diagnosis (table 1- continuation)
| 1 | 2 | 3 | 4 |
Age, y | 82 | 32 | 69 | 35 |
WBC ×109/L | 5,53 х10х9/L
| 6,23х10х9/L
| 10,25х10х9/L
| 0,840 х10х9/L
|
Hemoglobin, g/dL | 12,4 | 11,6 | 10,7 | 6,6 |
Platelet count ×109/L | 178,0 | 294,0 | 120,0 | 41,0 |
LDH, U/L | 322 | 196 | 410 | 317 |
IGHV mutation status | It is not possible to establish | Unmutated | Unmutated
| It is not possible to establish |
FISH | Normal | Normal | Normal | Normal |
Mutation TP53 | No mutations . | No mutations | No mutations | No mutations |
Mutation NOTCH1 | - | Mutation c7544 | No mutation | No mutation |
RS prognosis score | 2 (Intermediate) | 1 (Low) | 2 (Intermediate) | 1 (Low) |
Duration of acalabrutinib therapy (mon) | 15 | 12 | 15 | 5 |
Best response | PR | CR | Clinical benefit | PR |
Status at most recent follow-up | Аcalabrutinib therapy continues | Аcalabrutinib therapy continues | Death | Аcalabrutinib therapy continues |
Conclusion
our experience with these patients suggests that acalabrutinib in combination with immunochemotherapy has potential as a novel therapeutic approach for patients with Richter syndrome.
Keyword(s):