Thank you for posting Nancy. It’s interesting that the Venclexta monotherapy had such a good response with low toxicity. I’m hopeful that the a Venclexta, Kyprolis, and dexamethasone triplet will do a an even more effective job.
Thanks BN!
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Re: My Venclexta, Kyprolis & dex treatment experience
Hi Bar-None,
This presentation from ASH 2018 reports on a clinical trial such as the one you are on. The results seemed quite promising. Hopefully you will also achieve good results on this protocol.
"Phase 2 Study of Venetoclax Plus Carfilzomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma," ASH 2018 abstract 303.
Introduction: Venetoclax (Ven), an oral agent that targets the antiapoptotic protein, BCL-2, has demonstrated efficacy, as monotherapy and combined with proteasome inhibitor (PI) bortezomib, in relapsed/refractory (R/R) multiple myeloma (multiple myeloma). We report preliminary safety and efficacy data for Ven combined with the second generation PI carfilzomib (K) and dexamethasone (VenKd) in R/R multiple myeloma.
Methods: In this ongoing phase 2, dose escalation study (NCT02899052), patients with R/R multiple myeloma and no prior K exposure received VenKd on 28-d cycles in 4 dose finding and one expansion cohorts: Ven 400 mg/day + K 27 mg/m2 Day 1, 2, 8, 9, 15, 16 + dex 40 mg Day 1, 8, 15, 22 (Cohort 1), same regimen but with Ven 800 mg/day (Cohort 2), Ven 800 mg/day + K 70 mg/m2 Day 1, 8, 15 + dex 40 mg Day 1, 8, 15, 22 (Cohort 3/expansion cohort), or Ven 800 mg + K 56 mg/m2 Day 1, 2, 8, 9, 15, 16 + dex 40 mg Day 1, 2, 8, 9, 15, 16, 22, 23 (Cohort 4). Treatment continued until progressive disease (PD) or unacceptable toxicity.
Results: As of June 11, 2018, 42 patients were enrolled. The median age was 66.5 years (min, max: 37, 79), 63% had ISS II/III disease, and 8 patients (19%) had t(11;14). Patients received a median of 2 prior therapies (range: 1 – 3), 93% had received prior PI (50% refractory), 62% were refractory to immunomodulatory therapies, and 33% double refractory.
At the data cut off, 29 patients were still active and had completed ≥2 cycles and 13 patients discontinued with the primary reason being disease progression (n=4), death (n=3), physician decision (n=2), withdrawal of consent (n=2), lack of efficacy (n=1), and AE (n=1). All patients experienced at least one AE, and grade 3/4 AEs experienced by >10% of subjects included: decreased lymphocyte count (26%), decreased neutrophil count (14%), and hypertension (12%). Thirteen subjects experienced at least one serious AE. Maximum tolerated dose was not reached and Ven 800 mg/day + K 70 mg/m2 was selected for expansion. Ven mean (% coefficient of variation) maximum plasma concentration (Cmax) and area under the plasma concentration-time curve over 24 hours (AUC24) on Cycle 1 Day 15 were 2.7 (57) mg/mL and 33.1 (54) mg×h/mL, respectively, at 400 mg venetoclax (n=4); and were 2.42 (53) mg/mL and 38.7 (51) mg×h/mL, respectively, at 800 mg venetoclax (n=13) in the dose escalation cohorts.
The overall response rate (ORR) was 78% and the very good partial response (VGPR) or better rate was 56% (Table). Median time from first dose to the data cut or discontinuation was 5.7 months (range: 0.9 - 16.3) and the median time to first response was 1.9 months (95% CI: 0.9, 9.2). ORRs for subgroups of interest are reported in the Table.
Conclusions: The combination of VenKd appears tolerable with no new safety signals or changes in Ven pharmacokinetics. VenKd shows promising preliminary efficacy in R/R multiple myeloma patient subgroups. Response rates were comparable in all high risk subgroups and overall population. However, the subset of patients with t(11;14) had the highest response. Overall, these results demonstrate that VenKd is a safe and efficacious regimen in R/R multiple myeloma and support the continued study of VenKd.
https://ash.confex.com/ash/2018/webprogram/Paper117026.html
This presentation from ASH 2018 reports on a clinical trial such as the one you are on. The results seemed quite promising. Hopefully you will also achieve good results on this protocol.
"Phase 2 Study of Venetoclax Plus Carfilzomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma," ASH 2018 abstract 303.
Introduction: Venetoclax (Ven), an oral agent that targets the antiapoptotic protein, BCL-2, has demonstrated efficacy, as monotherapy and combined with proteasome inhibitor (PI) bortezomib, in relapsed/refractory (R/R) multiple myeloma (multiple myeloma). We report preliminary safety and efficacy data for Ven combined with the second generation PI carfilzomib (K) and dexamethasone (VenKd) in R/R multiple myeloma.
Methods: In this ongoing phase 2, dose escalation study (NCT02899052), patients with R/R multiple myeloma and no prior K exposure received VenKd on 28-d cycles in 4 dose finding and one expansion cohorts: Ven 400 mg/day + K 27 mg/m2 Day 1, 2, 8, 9, 15, 16 + dex 40 mg Day 1, 8, 15, 22 (Cohort 1), same regimen but with Ven 800 mg/day (Cohort 2), Ven 800 mg/day + K 70 mg/m2 Day 1, 8, 15 + dex 40 mg Day 1, 8, 15, 22 (Cohort 3/expansion cohort), or Ven 800 mg + K 56 mg/m2 Day 1, 2, 8, 9, 15, 16 + dex 40 mg Day 1, 2, 8, 9, 15, 16, 22, 23 (Cohort 4). Treatment continued until progressive disease (PD) or unacceptable toxicity.
Results: As of June 11, 2018, 42 patients were enrolled. The median age was 66.5 years (min, max: 37, 79), 63% had ISS II/III disease, and 8 patients (19%) had t(11;14). Patients received a median of 2 prior therapies (range: 1 – 3), 93% had received prior PI (50% refractory), 62% were refractory to immunomodulatory therapies, and 33% double refractory.
At the data cut off, 29 patients were still active and had completed ≥2 cycles and 13 patients discontinued with the primary reason being disease progression (n=4), death (n=3), physician decision (n=2), withdrawal of consent (n=2), lack of efficacy (n=1), and AE (n=1). All patients experienced at least one AE, and grade 3/4 AEs experienced by >10% of subjects included: decreased lymphocyte count (26%), decreased neutrophil count (14%), and hypertension (12%). Thirteen subjects experienced at least one serious AE. Maximum tolerated dose was not reached and Ven 800 mg/day + K 70 mg/m2 was selected for expansion. Ven mean (% coefficient of variation) maximum plasma concentration (Cmax) and area under the plasma concentration-time curve over 24 hours (AUC24) on Cycle 1 Day 15 were 2.7 (57) mg/mL and 33.1 (54) mg×h/mL, respectively, at 400 mg venetoclax (n=4); and were 2.42 (53) mg/mL and 38.7 (51) mg×h/mL, respectively, at 800 mg venetoclax (n=13) in the dose escalation cohorts.
The overall response rate (ORR) was 78% and the very good partial response (VGPR) or better rate was 56% (Table). Median time from first dose to the data cut or discontinuation was 5.7 months (range: 0.9 - 16.3) and the median time to first response was 1.9 months (95% CI: 0.9, 9.2). ORRs for subgroups of interest are reported in the Table.
Conclusions: The combination of VenKd appears tolerable with no new safety signals or changes in Ven pharmacokinetics. VenKd shows promising preliminary efficacy in R/R multiple myeloma patient subgroups. Response rates were comparable in all high risk subgroups and overall population. However, the subset of patients with t(11;14) had the highest response. Overall, these results demonstrate that VenKd is a safe and efficacious regimen in R/R multiple myeloma and support the continued study of VenKd.
https://ash.confex.com/ash/2018/webprogram/Paper117026.html
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: My Venclexta, Kyprolis & dex treatment experience
Thanks Nancy for the ASH info. It is very encouraging and is exactly what my myeloma specialist shared with me. However I believe the phase 2 trial has many more participants now since there are 14 participants at my center (UAB in Alabama) alone.
I am happy to be participating, however it's good to know that there are also monoclonal antibodies available to us..
Best! BN
I am happy to be participating, however it's good to know that there are also monoclonal antibodies available to us..
Best! BN
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Bar-none - Who do you know with myeloma?: Me
- When were you/they diagnosed?: 3/14
Re: My Venclexta, Kyprolis & dex treatment experience
This week is an off week as far as the dex and Kyprolis infusion. I continue to take 800 mg of Venclexta daily. No adverse events to report.
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Bar-none - Who do you know with myeloma?: Me
- When were you/they diagnosed?: 3/14
Re: My Venclexta, Kyprolis & dex treatment experience
Labs: Turned in my 24-hour urine and gave about 10 tubes of blood.
Today begins Cycle 2. I received Aloxi (palonosetron), a long-acting anti-nausea medication lasting three to five days, and my usual Kyprolis infusion.
I was also given an EKG to check for potential heart issues resulting from Kyprolis.
My M-spike will take a day or two, but my kappa free light chain level dropped from 118 to 50.
All chemistry was normal otherwise.
Best! BN
Today begins Cycle 2. I received Aloxi (palonosetron), a long-acting anti-nausea medication lasting three to five days, and my usual Kyprolis infusion.
I was also given an EKG to check for potential heart issues resulting from Kyprolis.
My M-spike will take a day or two, but my kappa free light chain level dropped from 118 to 50.
All chemistry was normal otherwise.
Best! BN
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Bar-none - Who do you know with myeloma?: Me
- When were you/they diagnosed?: 3/14
Re: My Venclexta, Kyprolis & dex treatment experience
I received my new M-spike numbers today, and they are the same as the January numbers (1.19 g/dL), so they have stabilized. My doctor is happy with that, and we are hopeful that next month there will be a decrease.
Best! BN
Best! BN
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Bar-none - Who do you know with myeloma?: Me
- When were you/they diagnosed?: 3/14
Re: My Venclexta, Kyprolis & dex treatment experience
Hi BN,
I suspect you already know this, but your serum free light chain numbers are likely to respond more quickly to treatment than your paraprotein (M-spike). Free light chains hang around in your body for a much shorter time than immunoglobulins, including abnormal immunoglobulins such as those measured by your M-spike. The half life in your body of free light chains is much, much shorter (3-6 six hours) than the half life of immunoglobulins (1-3 weeks).
This means that changes in the number of myeloma cells in your body usually will be reflected more quickly in your free light chain results than your M-spike result.
So, if the drop in your kappa level was mirrored by a similar drop in your kappa / lambda ratio, which you really want to make sure to track, I'd say you are responding really well to your treatment.
Cheers!
I suspect you already know this, but your serum free light chain numbers are likely to respond more quickly to treatment than your paraprotein (M-spike). Free light chains hang around in your body for a much shorter time than immunoglobulins, including abnormal immunoglobulins such as those measured by your M-spike. The half life in your body of free light chains is much, much shorter (3-6 six hours) than the half life of immunoglobulins (1-3 weeks).
This means that changes in the number of myeloma cells in your body usually will be reflected more quickly in your free light chain results than your M-spike result.
So, if the drop in your kappa level was mirrored by a similar drop in your kappa / lambda ratio, which you really want to make sure to track, I'd say you are responding really well to your treatment.
Cheers!
Re: My Venclexta, Kyprolis & dex treatment experience
Thanks Ian, I did not know that half lives were so different between light chains and the immunoglobulins. Thanks for sharing.
Best! BN
Best! BN
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Bar-none - Who do you know with myeloma?: Me
- When were you/they diagnosed?: 3/14
Re: My Venclexta, Kyprolis & dex treatment experience
This week I had Aloxi (palonosetron), Kyprolis, and Zometa. There was no adverse events to report other than still fighting a stubborn urinary tract infection. Currently I am on a course of Cipro 500 mg for one week and symptoms are improving.
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Bar-none - Who do you know with myeloma?: Me
- When were you/they diagnosed?: 3/14
Re: My Venclexta, Kyprolis & dex treatment experience
So happy to read that this is working for you! My mom is currently on week 3 of 400 mg Venclexta (venetoclax) only. Side effects have resolved and her numbers were almost cut in half.
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