1 00:00:00,040 --> 00:00:04,600 We will cover the second line really world change completely 2 00:00:04,600 --> 00:00:07,280 with Gardice cells. So Gardice cells now are in 3 00:00:07,280 --> 00:00:11,680 second line with laser cell and axis cell and then in the 4 00:00:11,720 --> 00:00:17,040 accommodation we propose axis and liser cell in second hand 5 00:00:17,040 --> 00:00:19,680 for patients eligible to cartice cells. 6 00:00:19,680 --> 00:00:23,120 So cartice cells are for patients in the collapse and 7 00:00:23,120 --> 00:00:27,800 refractory patients collapse within the first year and then 8 00:00:27,800 --> 00:00:30,560 for the patients that are not eligible for cartice cells 9 00:00:30,760 --> 00:00:35,360 Glofigermux or if you are collapsing really late, you may 10 00:00:35,360 --> 00:00:38,440 eventually challenge the patients with chemotherapy again 11 00:00:38,720 --> 00:00:43,120 and high dose therapy. Please autologous same as home 12 00:00:43,120 --> 00:00:49,280 conditions welcome. To EHE Unplugged, the official 13 00:00:49,280 --> 00:00:51,920 podcast channel from the European Hematology Association 14 00:00:51,920 --> 00:00:54,120 EHE. In this episode we are joined by 15 00:00:54,120 --> 00:00:57,800 Professor Maya Jose Kirsten from Amsterdam University Medical 16 00:00:57,800 --> 00:01:00,280 Center. I'm by Professor Catherine 17 00:01:00,280 --> 00:01:02,840 Teblumun from the Hospitals Only in Paris. 18 00:01:03,000 --> 00:01:06,680 Together, they will discuss the recently published EHA guideline 19 00:01:06,680 --> 00:01:09,720 for the diagnosis, treatment, and follow up of patients with 20 00:01:09,960 --> 00:01:13,480 large B cell lymphoma, LBCL. They're here to give you an 21 00:01:13,480 --> 00:01:16,360 overview of the guidelines and help you navigate the panel's 22 00:01:16,360 --> 00:01:18,880 recommendations. Welcome and enjoy this episode. 23 00:01:19,080 --> 00:01:21,880 Hello, I'm Catherine Tibermo from Paris Sunway Hospital. 24 00:01:21,920 --> 00:01:24,000 Hi. I'm Maria J Kirsten. 25 00:01:24,120 --> 00:01:27,080 I'm from Amsterdam. We worked together very hard to 26 00:01:27,080 --> 00:01:29,760 get this guideline on. We'll discuss all the insurance 27 00:01:29,760 --> 00:01:32,560 and outs of the guideline. So this is guidelines about 28 00:01:32,560 --> 00:01:38,800 largely selling from us and the first step for the the work up 29 00:01:38,840 --> 00:01:42,840 of the patients is about staging the patients. 30 00:01:42,840 --> 00:01:47,080 So, so how do we stage the patients for large B cell 31 00:01:47,080 --> 00:01:50,440 lymphoma? The first thing is to base the 32 00:01:50,440 --> 00:01:54,400 strategies based on the IPI. So we still use this 33 00:01:54,680 --> 00:01:59,640 international pomastic index based on the five factors. 34 00:02:00,360 --> 00:02:04,960 So the age of the patients which is really important, the 35 00:02:04,960 --> 00:02:10,320 interest level, the stage, the number of external sites and the 36 00:02:10,320 --> 00:02:14,040 performance status and the performance status is really the 37 00:02:14,040 --> 00:02:18,400 key to stratify the patients regarding the choice of the 38 00:02:18,400 --> 00:02:21,880 treatment that we will administer to the patients and 39 00:02:21,880 --> 00:02:26,120 make a choice. So the three key factors are 40 00:02:26,280 --> 00:02:30,840 age, personal status and extensions of the disease with 41 00:02:31,120 --> 00:02:35,160 the stage, the external sites and the number of these external 42 00:02:35,160 --> 00:02:36,000 sites. Yeah. 43 00:02:36,320 --> 00:02:39,440 And if we go a step back, because of course first we need 44 00:02:39,440 --> 00:02:43,760 a diagnosis, so we recommend excision of a lymph node. 45 00:02:43,840 --> 00:02:46,000 I think we had a lot of discussion about that. 46 00:02:46,000 --> 00:02:49,840 What's your opinion? Should we do needle biopsies or 47 00:02:49,840 --> 00:02:51,360 should we excise a whole lymph now? 48 00:02:51,560 --> 00:02:55,960 So there is a different school, schools for that and the 49 00:02:55,960 --> 00:03:01,400 technosis is of course based on this biopsy either which was the 50 00:03:01,400 --> 00:03:05,440 surgery or the core needle biopsy. 51 00:03:06,280 --> 00:03:11,120 This is a really easy to take the second strategy and to have 52 00:03:11,120 --> 00:03:15,880 a coordinated biopsy, really easy to get peripheral biopsy, 53 00:03:15,880 --> 00:03:20,960 peripheral leaf node biopsy, profound sites for the biopsy. 54 00:03:21,120 --> 00:03:24,760 And this is I think better compared to the surgery. 55 00:03:24,960 --> 00:03:28,520 Why? Because the surgery make make 56 00:03:29,200 --> 00:03:33,240 will take longer time to get the diagnosis and sometimes we do 57 00:03:33,240 --> 00:03:38,840 not have this time when we treat aggressive disease such as large 58 00:03:38,840 --> 00:03:41,720 be selling from us. If if possible and not too 59 00:03:41,720 --> 00:03:45,120 difficult to reach, I think a whole lymph node is probably 60 00:03:45,280 --> 00:03:47,080 better. Gives you more information on 61 00:03:47,080 --> 00:03:48,920 the architecture. Yes, yes. 62 00:03:49,600 --> 00:03:52,080 So, yeah. And particularly the micro 63 00:03:52,080 --> 00:03:56,440 environment, we know that with the new drugs now we need to 64 00:03:56,440 --> 00:03:59,560 have informations regarding the micro environments. 65 00:03:59,680 --> 00:04:04,840 It's always better to have this surgery biopsy, but if it's not 66 00:04:04,840 --> 00:04:09,640 possible, of course coordinated biopsy is really important and 67 00:04:09,640 --> 00:04:11,440 important step. And what do you think are the 68 00:04:11,440 --> 00:04:15,560 minimal methods that need to be used to get to a diagnosis at 69 00:04:15,560 --> 00:04:18,320 this point? Which methods, immunochemistry 70 00:04:18,320 --> 00:04:20,560 or molecular methods are really necessary? 71 00:04:20,680 --> 00:04:24,720 Yes, of course we need to have between high grade B cell 72 00:04:24,720 --> 00:04:29,720 lymphoma transform from indolent lymphoma as follicular 73 00:04:29,720 --> 00:04:33,760 meshalzone lymphoma as primary B cell lymphoma that are really 74 00:04:34,000 --> 00:04:36,920 particular lymphoma. So we need to have 75 00:04:37,160 --> 00:04:40,640 immunochemistry. We need to have also FISH 76 00:04:41,880 --> 00:04:48,560 diagnosis regarding genes such as Mick B cell 2B cell 6 and to 77 00:04:48,560 --> 00:04:55,000 have eventually the subtypes regarding ABC or GCB which is 78 00:04:55,240 --> 00:05:00,480 not now considered as nobligratory marker because we 79 00:05:00,480 --> 00:05:04,400 know that there is no difference in term of therapy strategies 80 00:05:04,400 --> 00:05:08,120 between AB, CS and GCBS largely selling from. 81 00:05:08,120 --> 00:05:12,280 What do you think of NGS to look at mutational landscape in the 82 00:05:12,280 --> 00:05:15,120 tumor cells? Yes, it's really important and 83 00:05:15,200 --> 00:05:18,560 interesting to have these markers, but right now we have 84 00:05:18,640 --> 00:05:23,280 no difference in term of therapy strategies based on NGS. 85 00:05:23,840 --> 00:05:28,120 I think that we will see more evidence of targeted agents 86 00:05:28,120 --> 00:05:32,560 being more more active for example in the MCD type is, but 87 00:05:32,680 --> 00:05:35,880 this is at the moment not we didn't make it part of of the 88 00:05:35,880 --> 00:05:38,120 guideline because it's not black and white. 89 00:05:38,120 --> 00:05:41,400 So we, yeah, we cannot do this in an evidence base then? 90 00:05:41,560 --> 00:05:44,440 Exactly. Maybe in the next round of the 91 00:05:45,160 --> 00:05:47,800 the guidelines, maybe in the future, in the near future. 92 00:05:47,960 --> 00:05:49,480 I'm sure not right now. Yeah. 93 00:05:49,720 --> 00:05:53,320 And what do you think is the strategy in terms of imaging 94 00:05:53,640 --> 00:05:58,160 diagnosis and for AS into a more end of treatment evaluation? 95 00:05:58,280 --> 00:06:00,560 Yes. So as we said at the baseline, 96 00:06:00,560 --> 00:06:06,200 it's really important to have a good aspect on the extension of 97 00:06:06,200 --> 00:06:10,880 the disease and even the master bulky and to measure the bulky 98 00:06:10,920 --> 00:06:15,640 more than based on the CT scan. But also the PET scan may afford 99 00:06:15,720 --> 00:06:21,760 to have a better evaluation of this bulky mass PET scan at the 100 00:06:21,760 --> 00:06:24,920 baseline. And then the PET scan may also 101 00:06:24,920 --> 00:06:30,840 be repeated with interim analysis after 2 cycles, 4 102 00:06:30,840 --> 00:06:33,920 cycles, and even at the end of the treatment. 103 00:06:33,920 --> 00:06:38,240 So if you are doing interim analysis, you may eventually 104 00:06:38,240 --> 00:06:42,800 skip at the end of the treatment with PET scan and only do ACT 105 00:06:42,920 --> 00:06:45,720 scan. But it's really important to 106 00:06:45,720 --> 00:06:50,120 have a sense of the metabolic response assessment, which is 107 00:06:50,280 --> 00:06:53,880 really important to know if we have complete response. 108 00:06:56,640 --> 00:07:00,640 Do you think that there is several aspect to assess this 109 00:07:00,640 --> 00:07:03,000 metabolic response in term of the? 110 00:07:03,520 --> 00:07:05,080 Yeah. So at the moment I think 111 00:07:05,080 --> 00:07:09,640 standard is that we use the Oval scores or the semi sort of semi 112 00:07:09,640 --> 00:07:14,160 quantitative assessment of the yeah, several shades of Gray. 113 00:07:14,160 --> 00:07:18,000 So and I think that for the moment is satisfactory. 114 00:07:18,000 --> 00:07:22,280 But I think for interim pets we might also start implementing 115 00:07:22,280 --> 00:07:26,360 the delta SUV because it has been shown that if at interim 116 00:07:26,360 --> 00:07:30,840 pets there is more than 70% decrease in the standardized 117 00:07:30,840 --> 00:07:33,520 uptake value, those patients have an especially good 118 00:07:33,840 --> 00:07:36,400 prognosis. I don't think that's implemented 119 00:07:36,400 --> 00:07:39,840 at the moment at most of the hospitals, but I definitely 120 00:07:39,840 --> 00:07:44,800 think Delta SUV and at diagnosis the metabolic tumor volume will 121 00:07:45,280 --> 00:07:47,520 gain the momentum in the coming years. 122 00:07:47,800 --> 00:07:53,160 This effectively is the strategy to evaluate better the patients 123 00:07:53,560 --> 00:07:56,640 during the first line. And so in your opinion what is 124 00:07:56,640 --> 00:08:00,040 the first line treatment for the patients with large B cell in 125 00:08:00,040 --> 00:08:01,960 from us? So the common patients, what is 126 00:08:01,960 --> 00:08:03,840 the best treatment for large B cell? 127 00:08:03,840 --> 00:08:05,760 Yeah. So depends of course on stage. 128 00:08:05,800 --> 00:08:10,400 So for the limited stage patients and low risk factors, I 129 00:08:10,400 --> 00:08:12,760 think abbreviated immunochemotherapy is the 130 00:08:12,760 --> 00:08:15,800 standard. So mostly 4 cycles of Archo. 131 00:08:16,080 --> 00:08:19,320 Maybe we can even go lower with the negative interim path. 132 00:08:19,480 --> 00:08:23,600 But for the stage 2 with Milky disease or stage 3, four, we, I, 133 00:08:23,680 --> 00:08:26,040 I remember we had some discussion about what was the 134 00:08:26,040 --> 00:08:28,880 best first line. And of course again depends on 135 00:08:28,880 --> 00:08:32,360 age, performance status, but also on comorbidities, for 136 00:08:32,360 --> 00:08:35,880 example, the cardio cardiacomorbidities, which would 137 00:08:35,880 --> 00:08:38,679 make treatment with antracyclins more difficult. 138 00:08:39,000 --> 00:08:43,240 But for the standard patients with a low IPI zero to 1, I 139 00:08:43,240 --> 00:08:47,760 think Archop 6 cycles is still the standard of care for, I 140 00:08:47,760 --> 00:08:52,280 don't know now 25 years or more. So we know perfectly effectively 141 00:08:52,280 --> 00:08:56,120 this surface line and based on Archop, what about the high 142 00:08:56,120 --> 00:09:00,480 grade piece of lymphoma because we know that Archop is maybe not 143 00:09:00,480 --> 00:09:02,480 so satisfactory for these patients? 144 00:09:03,000 --> 00:09:05,440 Yeah. So I create lymphomas especially 145 00:09:05,600 --> 00:09:09,080 if they are double hit. And as you know now in the new 146 00:09:09,400 --> 00:09:12,640 DHL classification, this pertains to patients who have a 147 00:09:12,640 --> 00:09:17,040 mid translocation and BCL 2 and it's no longer the MIC and BCL 6 148 00:09:17,200 --> 00:09:20,080 or the triple hits. I think they're with regular 149 00:09:20,080 --> 00:09:23,960 Archop we don't see a good enough outcomes and also the 150 00:09:24,000 --> 00:09:28,200 Polar R chip doesn't seem to be better than our shop in that 151 00:09:28,200 --> 00:09:31,320 particular population. So there we would go in a fit 152 00:09:31,320 --> 00:09:35,840 patient for those just epoch R or another intensified regimen 153 00:09:36,040 --> 00:09:38,880 and also strongly consider CNS prophylaxis. 154 00:09:39,680 --> 00:09:45,400 What about what is your opinion regarding this treatment and to 155 00:09:45,600 --> 00:09:47,720 whom? I would like to administer this 156 00:09:47,720 --> 00:09:50,760 treatment. So in the study, the patients 157 00:09:51,320 --> 00:09:55,360 with an IPI of two to five were eligible for for this study. 158 00:09:55,360 --> 00:09:58,560 So it's a higher risk population and there was a difference in 159 00:09:58,720 --> 00:10:03,600 progression free survive also 6% absolute difference, but no 160 00:10:03,600 --> 00:10:07,200 difference in overall survival, probably because we have good 161 00:10:07,200 --> 00:10:11,800 selfish salvage options with stem cell transplant or Carty in 162 00:10:11,800 --> 00:10:14,480 a second line. So yeah, it's implemented 163 00:10:14,480 --> 00:10:16,320 differently in different countries. 164 00:10:16,440 --> 00:10:19,400 For example in the Netherlands, but I think also in France, 165 00:10:19,400 --> 00:10:22,880 EFOLA is not reimbursed. So we still give our job. 166 00:10:23,040 --> 00:10:27,560 And the last question regarding the first line, but we could 167 00:10:27,560 --> 00:10:31,480 have a lot of more questions. What about this external 168 00:10:31,480 --> 00:10:34,640 disease? Sometimes we have patients with 169 00:10:35,240 --> 00:10:39,920 no involvement or few another involvement but external with 170 00:10:39,920 --> 00:10:44,800 testes for example. And we discussed the past few 171 00:10:44,800 --> 00:10:50,280 years about CNS prophylaxis. So how could we deal with this 172 00:10:50,280 --> 00:10:52,400 prophylaxis and external disease? 173 00:10:52,680 --> 00:10:54,760 I think that's a whole topic on itself. 174 00:10:55,400 --> 00:11:00,040 So much discussion about the use of CNS prophylaxis. 175 00:11:00,280 --> 00:11:03,080 I think most centers have abandoned intrathecal 176 00:11:03,480 --> 00:11:05,200 prophylaxis. So if you think there's an 177 00:11:05,400 --> 00:11:09,720 indication for CNS prophylaxis, I would go for high dose 178 00:11:09,720 --> 00:11:12,720 methotrexate. So at least three grams per 179 00:11:12,720 --> 00:11:16,120 meter square and two cycles and mostly do it at the end of 180 00:11:16,120 --> 00:11:18,240 therapy if there's no CNS involvement. 181 00:11:18,360 --> 00:11:23,640 And of course, it needs patient to do a baseline CSF assessment. 182 00:11:23,680 --> 00:11:27,000 And yeah, so if you look at the extranodal lymphomas, I think 183 00:11:27,000 --> 00:11:31,040 it's best demonstrated for primary testicular lymphoma 184 00:11:31,040 --> 00:11:34,280 because they have a very high rate of secondary CNS 185 00:11:34,280 --> 00:11:37,440 involvement. So we would definitely do it in 186 00:11:37,440 --> 00:11:41,120 those patients. I think the indication for CNS 187 00:11:41,120 --> 00:11:44,240 prophylaxis has shrinked over the years. 188 00:11:44,520 --> 00:11:46,840 And finally, the last one, because I think it's really 189 00:11:46,840 --> 00:11:48,680 important. The strategy is really different 190 00:11:48,680 --> 00:11:52,080 from the other large B cell. Lymphoma is the primary media 191 00:11:52,080 --> 00:11:57,840 cell lymphoma. What is your strategy for this 192 00:11:58,240 --> 00:11:59,400 PMBA? Yeah. 193 00:11:59,840 --> 00:12:01,600 Yeah. So these are mostly young female 194 00:12:01,600 --> 00:12:04,640 patients who present with a bulky mediastinal mass. 195 00:12:04,640 --> 00:12:09,480 And of course also here direct direct comparison in clinical 196 00:12:09,480 --> 00:12:12,400 trials is lacking mostly. But if you look at the results 197 00:12:12,400 --> 00:12:17,120 of ARCHOP versus intensified ARCHOP like ARCHOP 14 or those 198 00:12:17,120 --> 00:12:20,040 adjusted EPOCH R or other intensified regimens, there's a 199 00:12:20,040 --> 00:12:22,920 clear difference in the progression free survival in 200 00:12:22,920 --> 00:12:25,880 those patients and also very importantly, the rate of 201 00:12:25,880 --> 00:12:29,320 complete metabolic remission at the end of the induction. 202 00:12:29,520 --> 00:12:32,440 And that's really important because in those patients who 203 00:12:32,440 --> 00:12:36,280 still have active disease, you might consider the radiation 204 00:12:36,280 --> 00:12:39,480 therapy, but these are young female patients and giving them 205 00:12:39,480 --> 00:12:42,760 radiation therapy to the chest might also mean an increased 206 00:12:42,760 --> 00:12:46,000 risk for breast cancers. I think achieving the CMR is 207 00:12:46,040 --> 00:12:48,320 really important. I think the i.e. 208 00:12:48,320 --> 00:12:51,720 LSG did a great job in their study demonstrating that in 209 00:12:51,720 --> 00:12:56,560 patients with CMR you don't need radiation therapy and that this 210 00:12:56,560 --> 00:13:00,200 is achieved much more often with intensified recommends. 211 00:13:00,480 --> 00:13:04,120 That was interesting to see that actually our Job 14 performed 212 00:13:04,120 --> 00:13:07,240 more or less the same as even more intensive regimen. 213 00:13:07,240 --> 00:13:11,560 So we have started to we did those just at ebook R, but are 214 00:13:11,720 --> 00:13:14,760 drifting back to our job 14. How about your SO? 215 00:13:14,800 --> 00:13:17,200 This is exactly the same strategy. 216 00:13:17,360 --> 00:13:20,160 We know you, we are using our job 14. 217 00:13:20,320 --> 00:13:24,480 It's really easy and in this population of patients who are 218 00:13:24,560 --> 00:13:31,640 younger after 14 is really and there is no sort of effect, 219 00:13:32,160 --> 00:13:34,600 major sort of effect. So yes, we are. 220 00:13:35,120 --> 00:13:39,760 We switch the two after 14. Yeah, in the primary B cell in 221 00:13:39,760 --> 00:13:40,720 format. Yeah. 222 00:13:40,720 --> 00:13:44,160 And then what do you do in the patients who still have no CMR, 223 00:13:44,160 --> 00:13:46,760 so either the score four or five? 224 00:13:46,800 --> 00:13:51,880 So we can create as you said delta SUV here to be sure that 225 00:13:51,920 --> 00:13:57,240 we are really in not a good response and then we biopsy, we 226 00:13:57,240 --> 00:14:01,480 try to biopsy the patients and we go to second line if we are 227 00:14:01,480 --> 00:14:04,240 not in. Complete response. 228 00:14:04,240 --> 00:14:06,200 Yeah. So you wouldn't go for radiation 229 00:14:06,360 --> 00:14:10,680 in those patients? We prefer depending on how is 230 00:14:10,680 --> 00:14:14,280 the hazardous disease if you have minimal hazardous disease 231 00:14:14,800 --> 00:14:20,800 with many I mean a small sites still involved and if 232 00:14:20,800 --> 00:14:25,400 hyperfixation we may eventually propose a radiation therapy, but 233 00:14:25,600 --> 00:14:29,000 if we have no chemo sensitivity, we will move to. 234 00:14:30,840 --> 00:14:32,840 Yeah, I agree. And I think in this in this 235 00:14:32,840 --> 00:14:38,040 study that I'll study, they also showed that if you irradiate 236 00:14:38,040 --> 00:14:41,640 this DOFIO score 4 cases and there's also a very good 237 00:14:41,640 --> 00:14:44,320 response. But another strategy is just to 238 00:14:44,320 --> 00:14:47,600 wait and repeat the PET scan. Exactly this, yeah. 239 00:14:47,840 --> 00:14:49,840 Yeah, I think we've covered the first line. 240 00:14:49,840 --> 00:14:53,840 And then we will shortly cover the second line that we had 241 00:14:54,200 --> 00:14:57,480 really world that change completely with the gardice 242 00:14:57,480 --> 00:14:59,440 cells. So Gardice cells now are in 243 00:14:59,440 --> 00:15:02,480 second line with laser cell and axis cell. 244 00:15:02,640 --> 00:15:08,200 And then in the accommodation we propose axis cell, laser cell in 245 00:15:08,200 --> 00:15:11,720 second line for patients eligible to CARTES cells and 246 00:15:11,720 --> 00:15:15,920 then for the patient that are not eligible for Cartes cells 247 00:15:15,960 --> 00:15:19,600 and collapsing. So Cartes cells are for patients 248 00:15:20,080 --> 00:15:24,520 in the collapse and refractory patients collapse within the 249 00:15:24,520 --> 00:15:27,880 first year and then for the patients that are not eligible 250 00:15:27,880 --> 00:15:32,680 to for cartesis glaufygmarks or if you're collapsing really 251 00:15:32,680 --> 00:15:35,480 late, you may eventually challenge the patients with 252 00:15:35,480 --> 00:15:40,080 chemotherapy again and high dose therapy plus orthologous 253 00:15:40,280 --> 00:15:44,080 symptoms transportations. So the choice for this online is 254 00:15:44,080 --> 00:15:50,040 really depending on the time of collapse and the sense of how 255 00:15:50,040 --> 00:15:55,000 refractory the disease is regarding chemotherapy. 256 00:15:55,240 --> 00:15:57,200 Yeah. So in the in different countries 257 00:15:57,200 --> 00:16:00,760 this is weighed a little bit differently by also by the HCA 258 00:16:00,960 --> 00:16:02,760 bodies. And for example in the 259 00:16:02,760 --> 00:16:06,480 Netherlands, the patients in the second line who are refractory 260 00:16:06,480 --> 00:16:10,720 or who have early relapse should be transplants eligible to 261 00:16:10,800 --> 00:16:13,920 receive CAR T, which I think is a little strange because they're 262 00:16:13,920 --> 00:16:15,880 not getting high dose chemotherapy. 263 00:16:15,880 --> 00:16:18,920 So they should be eligible for car DI think and not for stem 264 00:16:18,920 --> 00:16:22,440 cell transplant. But yeah, hopefully there will 265 00:16:22,440 --> 00:16:27,320 be the results of the daily two study and we can re discuss this 266 00:16:27,320 --> 00:16:31,240 also with with our healthcare institute in France. 267 00:16:31,880 --> 00:16:33,200 It's not a problem. You can. 268 00:16:33,280 --> 00:16:37,920 Yes, we can effectively use this strategy for how the patients in 269 00:16:38,120 --> 00:16:41,360 early relapse. And then the Sol line that is 270 00:16:41,560 --> 00:16:45,040 really improving with the bispecific antibodies, anti 271 00:16:45,040 --> 00:16:50,200 CD20, anti CD3 with two antibodies available in Europe 272 00:16:50,200 --> 00:16:54,960 and almost all over the world with glofetamab and apreitamabs 273 00:16:54,960 --> 00:16:59,680 of both drugs that are changing. Also the result in third line 274 00:16:59,680 --> 00:17:03,480 for patients with refractory disease after two prior lines. 275 00:17:03,520 --> 00:17:05,319 Yeah. I think in this context, it's 276 00:17:05,319 --> 00:17:09,319 interesting the effort which was done by Florence Prusa together 277 00:17:09,319 --> 00:17:12,040 with the guidelines. We also actually published their 278 00:17:12,040 --> 00:17:16,880 perspective paper in Hemisphere, which was led by Florence. 279 00:17:16,880 --> 00:17:20,079 Actually looking at the availability of all those new 280 00:17:20,079 --> 00:17:24,000 drugs in Europe. She has shown some, I think more 281 00:17:24,000 --> 00:17:27,359 shocking results about clinical trial availability, which is all 282 00:17:27,400 --> 00:17:30,160 very different between a different European country, but 283 00:17:30,160 --> 00:17:34,720 also to access in terms of reimbursement to these new drugs 284 00:17:35,000 --> 00:17:37,920 because there are many countries including ours where for 285 00:17:37,920 --> 00:17:40,800 example, by specifics are not yet reimbursed. 286 00:17:41,160 --> 00:17:43,760 So we're seeing a completely different picture. 287 00:17:44,080 --> 00:17:46,360 Yeah, across, even across Europe, yeah. 288 00:17:47,240 --> 00:17:51,320 Thank you very much and thank you to everybody here to have 289 00:17:51,320 --> 00:17:54,280 listened to us about these guidelines of large be selling 290 00:17:54,280 --> 00:17:57,800 format guided by EHH. Thank you very much. 291 00:17:57,880 --> 00:17:59,600 And thank you to the audience for listening. 292 00:17:59,600 --> 00:18:02,960 And if you enjoyed this episode, please like it and subscribe to 293 00:18:02,960 --> 00:18:05,480 our channel. Stay tuned for more episodes of 294 00:18:05,480 --> 00:18:06,280 EH. Unplugged.